Surgery for PD - a Layman's Explanation
Last month, The Parkinson's Institute Auxiliary Bulletin had quite a bit of data
 of general interest, so I posted a copy here. This month, the Bulletin has
 mostly items of interest to members. It seemed, therefore, to be
a good time to bring you a series of three articles written by our contributing
 editor, David Rosner. David is the Institute's Administrative Manager and
 Medical Librarian. Most issues of the Auxiliary Bulletin carry an a
rticle of general interest by David.
 
PALLIDOTOMY - A LAYMAN'S EXPLANATION
 
by David Rosner, The Parkinson's Institute
 
INTRODUCTION
 
The pallidotomy is a neurosurgical procedure that involves insertion of a probe
 (a long needle) into a specific region of the brain known as the globus
 pallidus.  The neurosurgeon then activates the tip of the probe, purp
osfully damaging certain neurons that, in patients with Parkinson's disease,
 have become overactive.
 
The initial rationale for using this technique to treat Parkinson's disease
 derived from the observation in the 1930s that minor strokes in the globus
 pallidus in Parkinson's patients resulted in alleviation of tremor.  T
hus, it was theorized that using a probe to lesion (damage) this same area of
 the brain could reproduce the effects of the stroke.  However, the early
 results of this technique were variable and often fraught with surgica
l complications. One of the reasons for the rather poor results was the
 inability to accurately locate this rather small group of neurons.  With the
 introduction of stereotaxic surgery in the 1940s, the results improved.
 Stereotaxic surgery involves bolting a "frame" on the skull which provides
 fixed reference points for localizing a target in the brain.  This frame guides
 the surgeon, through the use of previously determined anatomic co
ordinates, in placing a probe to reach the desired neuronal cells.  Stereotaxic
 techniques made the process less "hit-and-miss" but still somewhat "blinded";
 it was still very difficult to specify the area that should be
lesioned for best results.  In addition, clinical trials for the procedure were
 rather poorly designed and documented. Thus, by the 1960s, use of the
 pallidotomy was beginning to diminish and was all but abandoned with th
e advent of levodopa therapy in the late 1960s.
 
THE MODERN AGE OF PALLIDOTOMIES
 
In 1985, Dr. Lauri Laitinen, a Swedish neurosurgeon, began lesioning the
 posteroventral part of the inner globus pallidus, building upon studies by
 another neurosurgeon (Dr. Leksell) and his colleagues.  Dr. Laitinen foun
d that lesioning this area relieved most of the symptoms of parkinsonism,
 including tremor, rigidity, and bradykinesia (slowness).  He reported that the
 improvement was sustained over time.  He also reported that on-off f
luctuations and levodopa-induced dyskinesias could be reduced in some patients.
 
In the early 1990s, Dr. Mahlon DeLong, a neurologist at Emory University in
 Atlanta, discovered that lesions of a small cluster of neurons called the
 subthalamic nucleus abolished tremor, bradykinesia and rigidity in the
MPTP monkey model of Parkinson's disease.  This discovery suggested that
 dopamine deficiency, which occurs in Parkinson's disease, causes neurons of the
 subthalamic nucleus to be overactive.  Since these neurons activate
the inner globus pallidus, these neurons are, in turn, overactive.  Further
 refinement of this work by DeLong and his colleagues led to the identification
 of specific neurons whose overactivity seem to cause many of the f
eatures of Parkinson's disease.  It turns out that the discharges from these
 neurons are unique and can be identified by a method called "single cell
 recording".  Researchers are now utilizing this neurophysiological meth
od to identify the exact area that will be lesioned.  Using a microelectrode
 probe that measures cellular activity, and by "listening" to the cells' pattern
 of discharge, the surgeon and surgical team are better able to p
lace the lesion in the desired area of brain for optimum results.  How can we
 listen to the cells discharge?  The inserted probe is specially designed to
 record and amplify the sounds made by the cells as the probe passes
 through the brain.  These neurophysiological techniques are augmented by
 improved imaging systems (computerized axial tomography [CAT] and magnetic
 resonance imaging [MRI]).  All of this information, when added to the im
proved anatomical coordinates provided by the stereotaxic frame, allows the
 neurosurgeon to pinpoint the precise cells to be lesioned.
 
The neurophysiological techniques mentioned above are still in the experimental
 stage.  Dr. Laszlo Tamas, who has been appointed Director of Functional
 Neurosurgery programs at the Parkinson's Institute, has extensive exp
erience with this technique.  He has used neurophysiological methods in treating
 patients with disabling tremor by placing precise lesions in the thalamus and
 has been active in the Institute's experimental studies on pal
lidotomies. As the number of centers providing pallidotomies as a treatment for
 Parkinson's disease has grown, anecdotal reports of dramatic improvement have
 been reported in the media and elswhere.  However, as of March,
 1995, not one report of a well-designed study of this procedure has been
 published.
 
What do we mean by a "well-designed study"?  It is commonly recognized that
 before a drug is placed on the market, a pharmaceutical firm is required by the
 Food and Drug Administration (FDA) to undertake a series of clini
cal drug studies starting with tolerability in animals and ending with a
 double-blind study in a large number of patients (usually a multi-centered
 study).  These double-blind studies are important to ensure that the effe
cts of the drug on a group of subjects are measured against a matched control
 group not receiving the drug.  This type of study eliminates three factors that
 can obscure interpretation of the study: 1) the placebo effect,
 2) subject bias, and 3) examiner bias.  With surgical therapies, there is no
 FDA equivalent that oversees the safety (i.e., efficacy and tolerability) of a
 given procedure.  Usually, the only regulatory body governing wh
ether or not a surgical procedure can be performed is the institution's own
 investigational review board (IRB).
 
Thus, carefully designed studies are essential for judging the surgical outcome
 and complications of any given surgical procedure. It is disturbing that in
 some centers literally hundreds of individuals have undergone a p
allidotomy and yet there has been no reliable assessment whereby other
 physicians can judge the value of the procedure.  For this reason, we are
 advising our patients to use caution in deciding on this procedure as a trea
tment.  In the near future, Dr. Tamas will be perfoming this procedure.  We are
 now completing a comprehensive protocol that ensures appropriate selection of
 patient for this procedure as well as pre-operative and post-op
erative assessment.  In this way, we hope to optimize the outcome of this
 treatment for our patients.  In addition, by carefully evaluating our patients
 post-operatively, we will hope to learn what features of Parkinson's
 improve, the length of improvement and the risks of surgery.
 
Our goal is to be performing pallidotomies on Parkinson patients before the end
 of 1995.  Much work needs to be done before we can get started - a hospital
 needs to be selected and an operating room must be outfitted with
 electrophysiological shielding and other specialized surgical equipment.
 Preliminary financial agreements and arrangements between the Parkinson's
 Institute and the hospital must be put in place, and the relationship be
tween the patient's insurance company must be defined, especially since we now
 have various "managed-care" and health maintenance organizations (HMO's) to
 deal with.  Most importantly, a protocol needs to be set up to ade
quately assess the results of a clinical trial of pallidotomies. This will help
 to ensure that patients are benefitted by this surgical procedure and will
 allow us to determine the duration of that benefit.  These steps a
re in progress and further updates will be given to you as soon as they are
 available.
 
ONE LAST NOTE
 
You are probably be aware that several private neurosurgeons and neurosurgeons
 at large medical institutions throughout California are already performing
 pallidotomies.  We will not critique other surgical programs, and w
ould not recommend one over another. Neither will we tell someone not to go
 somewhere for this procedure.  It is certainly tempting for a patient to go
 ahead and have someone else perform the procedure now, rather than wa
iting for the Parkinson's Institute and for research advances that will likely
 make the technique safer and possibly more beneficial. However, it certainly
 seems worthwhile to wait, for at least just a few more months, so
 that more information about the results of pallidotomies that have already been
 performed can be reported. Please consider having the person who will undergo
 this operation talk with his/her neurologist and get an inform
ed opinion - is the patient a good candidate for the pallidotomy?  Does the
 doctor feel this procedure will be beneficial for that patient?  What benefit
 would the doctor expect for the patient?  Getting an opinion from t
he patient's own doctor is better than relying on anecdotal information,
 newspaper reports or telephone surveys to determine whether an experimental
 surgical procedure is something you want to do.
 
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Next - Thalamotomy
*********************************************
 
THALAMOTOMY - A LAYMAN'S EXPLANATION
 
by David Rosner, The Parkinson's Institute
 
Last month, we started to explain various surgical approaches to
Parkinson's disease.  As noted in that article, there are four main
surgical approaches being investigated by Parkinson's researchers
today: 1) Pallidotomy, 2) Thalamotomy, 3) Stimulation of the
ventral intermedius nucleus (VIM) of the thalamus, and 4)
Transplantation of fetal tissue.
 
In this article, I'd like to try and give a layman's explanation of the
thalamotomy, which is used mostly to relieve tremor in patients with
Parkinson's disease and essential tremor.
 
THALAMOTOMY - RATIONALE AND THE PROCESS
 
The earliest mention of thalamotomy as a surgical procedure to
alleviate tremors dates back to 1906 when Dr. R.H. Clarke
described a stereotaxic instrument and procedure for lesioning the
brain. Dr. Clarke, working with Dr. Victor Horsley, did not specify
the lesioning of the thalamus.
 
Thalamotomies were actually first performed in the late 1940s by
Drs. Spiegel and Wycis and their colleagues, utilizing a stereotaxic
frame to identify the thalamus.  Why the thalamus?  The thalamus is
an area deep within the brain that coordinates the activity of motor
and sensory commands throughout the brain.  It is part of a major
neuronal "highway" which runs throughout the brain (i.e., cortex to
striatum to pallidum to thalamus and back to cortex).  Normally, this
"highway" runs smoothly as the neurons interact.  When this system
is working properly, signals are sent between these neurons,
allowing the brain to communicate with various parts of the body.
In patients with Parkinson's disease, because of the loss of
dopamine, an imbalance occurs in this system resulting in tremor,
slowing of movement and rigidity.
 
It has been known for decades that lesions placed in a specific
region of the thalamus can abolish tremor on the contralateral
(opposite) side of the body.  The target is located by recording cell
discharges from a microelectrode placed in the thalamus.  The
neurosurgeon and "neurophysiologist" who assists him then listen for
the tale-tell sound of the neurons that, when lesioned, will abolish
the tremor.  Once the target area is identified, the probe is heated
and the lesioning is accomplished.  The patient is usually awake and
communicating with the surgeon during this process.  It should be
noted that this procedure only benefits tremor and no other
symptom of Parkinson's disease.
 
WHO IS A CANDIDATE?
 
Since this procedure really only affects only tremor, those patients
with "tremor-predominant" Parkinson's disease whose tremor is not
adequately treated by antiparkinsonian medications would be
candidates.  This procedure also can benefit individuals with
essential tremor who lack sufficient response to medications.  The
thalamotomy is best limited to patients with young-onset Parkinson's
disease whose symptoms are confined to one side of the body (i.e.,
unilateral tremor).  This does not automatically exclude older subjects or
those with bilateral tremor; however, these patients may have more
risk of complications from the surgery, such as mental changes (i.e.,
confusion), impairment of speech and/or balance, swallowing
problems, etc. Recent advances in the technology for locating the
area to be lesioned has tended to reduce these complications.
 
RESULTS, AND A FEW FINAL NOTES
 
It is estimated that thalamotomy is effective in relieving 80-90% of
tremor in patients with Parkinson's disease and essential tremor.  It
may also help ease dyskinesias in patients experiencing these
movements due to antiparkinson medications.  Thalamotomy does
not relieve symptoms such as bradykinesia (slowness of
movement), postural instability or gait problems. It will also not stop
or slow the progression of Parkinson's disease.  Bilateral
thalamotomies can cause a profound impairment in speech and,
unless this complication can be avoided with novel surgical
techniques, only unilateral thalamotomies are recommended.
 
How do you decide whether you are a candidate?  Talk to the
doctor who treats your Parkinson's disease or essential tremor.
Make sure your doctor (i.e., internist, neurologist, etc.) is familiar
with thalamotomies, and can recommend a qualified surgeon.  It
may be advisable to get a second opinion from a neurologist
specializing in the diagnosis and treatment of movement disorders to
determine whether you are a good candidate for surgery (and to
help post-operatively in evaluating your response to the procedure).
 
The thalamotomy is generally regarded as a safe procedure, has
been performed for a good many years with success, and can result
in significant long-term benefit for a number of candidates.
However, it involves damaging neurons in order to cause a positive
effect.  This process cannot be reversed; patience and caution
should be exercised as you carefully research the operation and the
person who will be performing the actual surgery.
 
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Note: I wish to thank Dr. James Tetrud for his comments and
advice on this article.  I'd also like to thank (belatedly, I'm afraid)
Dr. Heidi Shale for her helpful comments and advice on last month's
article on pallidotomy.  Copies of both articles will be available from
the clinic staff for patients who would like general information on
these procedures.     David Rosner
***************************************************
NEXT - STIMULATION OF THE
VENTRAL INTERMEDIUS NUCLEUS (VIM)
OF THE THALAMUS
***************************************************
 
 
 
STIMULATION OF THE VENTRAL INTERMEDIUS
NUCLEUS OF THE THALAMUS - A LAYMAN'S
EXPLANATION
 
by David Rosner, The Parkinson's Institute
 
In past months, we have discussed two surgical approaches to
Parkinson's disease (Thalamotomy, and Pallidotomy).  As noted in
those articles, there are two other surgical approaches being
investigated by Parkinson's researchers today: 1) Stimulation of the
ventral intermedius nucleus (VIM) of the thalamus, and 2)
Transplantation of fetal tissue.
 
In this article, I'd like to try and give a layman's explanation of
Stimulation of the ventral intermedius nucleus (VIM) of the
thalamus, which is used almost exclusively in patients whose tremor
causes significant functional disability; generally, these patients have
little or no response to standard anti-parkinson medication.
Younger patients seem to have a better response to this treatment
but older patients can also be candidates.
 
THE PROCEDURE:
 
Just like in a thalamotomy, the patient has a stereotactic frame
bolted to his skull; this frame and a CT scan of the brain help to
locate the general area to be addressed.  The target (the VIM of the
thalamus) is pinpointed by recording cell discharges from a
microelectrode placed in the thalamus.  The neurosurgeon and
"neurophysiologist" who assists him then listen for the tell-tale sound
of the neurons that must be dealt with to abolish the tremor.  The
patient is usually awake and communicating with the surgeon during
this process.
 
Once the target area is identified in this operation, however, the
microelectrode probe is not heated so that lesioning is
accomplished; instead, the electrode is sutured into place in the
skull. Thin wires (which have to be implanted in the neck) connect
the electrode to the "impulse generator", a very small stimulator unit
which is placed under the skin of the chest region.  As I've seen it
described, the stimulator unit is sort of like a cardiac pacemaker,
except it's hooked up directly to the brain.  The device can last
between three and five years.
 
 
 
RESULTS:
 
For reasons researchers have not been able to explain, this VIM
stimulation has almost exactly the same effect as lesioning the
thalamus - tremor is almost completely abolished, and other motor
function seems to be restored.  It would seem that this operation is
much more positive, in that you don't have to permanently damage
the area of the brain for the patient to be helped. Of course, a
drawback is that you have to wear the "stimulator unit" in and on
your body all the time - it's not detachable for social occasions, for
example.  However, approximately 88% of the Parkinson patients
who have undergone this operation with Dr. Alim Benabid (the
French Professor who pioneered this technique over the past
twenty years) have reported major benefits. It is also helpful for
almost 70% of the patients with essential tremor and for other types
of tremor as well.
 
HOW DO I SIGN UP?
 
You're probably wondering why you haven't heard much about this
procedure before.  Well, it's still experimental and only being used
in controlled clinical trials at this time.  The Parkinson's Institute is
very aware of the procedure and is looking to get involved in a
clinical trial in the near future; this will probably happen once we
have selected a site (i.e., a local hospital) for all of our surgical work
on the various approaches we'd like to try.  We'll keep you posted.
 
 
OTHER NOTES:
 
I'm not going to try and explain the fetal tissue implantation
procedure for you - a better way to learn about it will be by
watching ABC's "PrimeTime Live" segment highlighting Dr.
Langston and Dr. Widner. Both Dr. Langston and Dr. Widner will
be explaining the fetal tissue operation on Connie Sainz, one of the
original MPTP-exposed subjects we've been following for years in
the Institute's clinical facility, and discussing the effects we've seen
so far.  It should be a very informative program, and if you miss it,
I'm sure the Institute will have a copy of the program available for
you to borrow and watch.
 
 
The Institute's latest newsletter just came out.  We hope (and plan) to
publish newsletters more often in the future and capture late-breaking
research information for our patients and friends.
 
 
                       Excerpted from
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       *            AUXILIARY  BULLETIN              *
       *  Distributed monthly to selected TPI Staff  *
       *         and all Auxiliary Members           *
       ***********************************************
Editor: Arvid Rosenboom     Contrib. Ed.:   David Rosner