Dear Ivan:

Please find a copy of an article written by Dr. Ron Alterman, the
neurosurgeon who performs the Pallidotomy procedure at NYU Medical Center, it
may help answer some of your questions.

Also, I can arrange for you to speak with a gentleman from Maine who had the
procedure in 1995.

I wish you the best,

Annie O'Sullivan
Administrator
NYU Center for the Study & Treatment of Movement Disorders


P.S.  The Learning Channel followed one of our patients during his
"Pallidotomy" experience which is scheduled to air on March 16th.  They met
with him before his surgery, followed him into the hospital and operating
room and interviewed him again a week after surgery. When I know the exact
time, I will announce it to the list.



Pallidotomy for Parkinson's Disease


The NYU Center for the Study and Treatment of Movement Disorders

 Introduction
 Parkinson's disease (PD) is a neurologic disorder in which the nerve cells
of the substantia nigra degenerate.  These neurons are special for two
reasons:  1- they are part of a brain system, the basal ganglia, which
modulates movement and 2- they use the chemical dopamine to communicate with
other neurons.  The death of these dopaminergic neurons leads to an imbalance
in the finely tuned basal ganlia system, resulting in a number of motor
disturbances.  Initially, this may be manifest as a mild tremor at rest, or
stiffness in one extremity.  With further degeneration, symptoms worsen and
become debilitating.  Stiffness, slowness of movement (bradykinesia), painful
muscle cramps, and freezing (akinesia) may all result, making it difficult
for the patient to perform such simple tasks as eating, walking, turning over
in bed, or getting dressed.  People's lives are destroyed.  Family members
watch helplessly as their loved one, once independent and vital, becomes
increasingly dependent on others.
 Early on, PD responds well to medications.  L-DOPA is the precursor molecule
from which dopamine is formed.  L-DOPA preparations such as Sinemet
supplement the dopamine loss, ameliorating many Parkinsonian symptoms for
many years.  Pergolide and bromocriptine mimic dopamine's effects by
stimulating the receptors in the brain to which dopamine normally binds.
 Eldepryl is believed to slow the process which leads to the death of the
dopaminergic cells.  These and other medications may be used alone, or in
combination, depending on the patient's response, the preference of the
treating physician, or other circumstances.  L-DOPA therapy, however, is the
mainstay of medical therapy for PD.  In fact, a poor initial response to
L-DOPA raises the possibility that the diagnosis of PD is incorrect.
 With time, the response to L-DOPA wanes.  Patients respond to the medication
less consistently and for shorter periods of time.  They begin to suffer from
medication side-effects, the so-called DOPA-induced dyskinesias (DID), and
experience worsening "on-off" fluctuations.  In the off state, these patients
are rigid and immobile.  They stare at the world with an expressionless
"mask-like" face; many cannot stand without assistance from a walker or cane.
 In the on state they are freer and have less tremor, but severe dyskinesias
neutralize the medication's positive effects.  For many, the dyskinesias are
worse than the PD, causing patients to limit the amount of medicine they take
or to discontinue their medication entirely.
 In the latter stages of the disease, patients may have terrible gait
imbalance and recurrent falls.  They respond poorly to medication and are
wheelchair bound.  Dopaminergic neurons in the frontal lobes of the brain may
also begin to degenerate causing a decline in cognitive abilities.




What is Pallidotomy?
 Pallidotomy is a neuroablative procedure in which a small part of the globus
pallidus, another part of the basal ganglia system, is destroyed.  Animal
models of PD have demonstrated that the loss of dopaminergic neurons causes
the internal segment of globus pallidus (GPi) to become too active.  This
hyperactivity is believed to be responsible, in large part, for the stiffness
and slowness experienced by Parkinson's patients, and may also contribute to
tremor.  By destroying part of GPi, the basal gangia system is "rebalanced"
alleviating many parkinsonian symptoms.  An unexplained benefit of
pallidotomy is that DID is also relieved.
 Pallidotomy is not a new procedure.  Neurosurgical pioneers including Irving
Cooper at NYU, developed the operation in the 1950's and 60's.  While their
results were encouraging, the complication rates were quite high, and the
procedure was abandoned in the late 1960's with the introduction of L-DOPA
therapy.  Over the last twenty-five years technological advances such as
magnetic resonance imaging (MRI), microelectrode recording (MER), advanced
stereotactic frames, and, of course, the computer revolution, have made it
possible for neurosurgeons to refine the pallidotomy technique, yielding
excellent therapeutic results and low complication rates.  These advances,
combined with the understanding that L-DOPA will not work forever, have led
to renewed interest in pallidotomy.  NYU has continued as a leader in this
work.

Indications for Pallidotomy
 Pallidotomy is not for everyone.  The primary goal of our work at the Center
for Movement Disorders has been to refine the indications for the procedure,
thereby reducing complications and avoiding surgery for those who will not
improve.
 Good candidates typically have had PD for 5-10 years during which time they
have been responsive to L-DOPA.  Their PD is asymmetric (ie. one side of
their body is affected more than the other).  They have a predominance of
stiffness, slowness, and muscle cramping; tremor is not their primary
problem.  In the on state they suffer from DID.  Younger patients tend to
respond better than older patients; however, no one is eliminated from
consideration based solely on their age.
 "Midline" symptoms do not usually respond well to pallidotomy.  These
include low voice volume, swallowing difficulty, unsteadiness, falls, and
freezing.  Resting tremor improves in some patients, but this is not the best
indication for the operation.
 Keep in mind that the above descriptions of good and poor indications are
presented for the sake of comparison.  Most individuals suffer from a
combination of symptoms some of which will improve with pallidotomy.  A
detailed discussion between the patient and surgeon is critical so that the
surgeon understands which symptoms are most bothersome to the patient and the
patient understands just what the operation will and will not do.  Only then
can an informed decision be made. This decision, of course, is made in light
of our clinical evaluation, the neuropsychological testing, and positron
emission tomographic (PET) results.

The Preoperative Workup
 Patients who are interested in undergoing pallidotomy at NYU must be
evaluated by Dr. Enrico Fazzini, our Parkinson's neurologist, and Dr. Ron
Alterman, our neurosurgeon.  A recent MRI of the head must be available to
rule out significant brain atrophy or other brain lesions.  Such findings may
eliminate a patient from consideration.   If Drs. Fazzini and Alterman agree
that the patient is potentially a good candidate for pallidotomy,
arrangements are made for preoperative neuropsychological testing and a PET
scan.
 Neuropsychological testing is performed by Dr. Ken Perrine or one of his
associates at the Hospital for Joint Diseases.  The tests typically take 2-3
hours to complete.  These are performed in order to rule out subtle memory
loss, an early sign of the dementia which may accompany PD.  We have found
that individuals with even subtle cognitive deficits are at increased risk
for having more severe cognitive difficulties following pallidotomy.  If
these early changes are discovered, we will not proceed with surgery.
 The final hurdle is the PET scan.  NYU is the only center in the world which
employs PET scan results in its clinical decision making.  In true PD, PET
scanning reveals the hyperactivity in GPi which I discussed in the
indtroduction.  We have demonstrated that patients without this hyperactivity
will not respond to pallidotomy and should not be operated.  Most important,
if the PET scan reveals too little activity in the region of GPi, the patient
may have one of the so-called "Parkinson's Plus" syndromes, rarer disorders
which resemble PD but involve more than the dopaminergic system.
 "Parkinson's Plus" syndromes do not improve with pallidotomy in our
experience.
 Once a patient is deemed a good candidate for the surgery, they are sent for
medical clearance and presurgical testing.  Assuming the patient has no
medical problems which make surgery unsafe, we proceed with the pallidotomy.

The Surgery
 Pallidotomy patients are admitted 2 days prior to surgery so that we may
complete the preoperative motor evaluation.  On the day prior to surgery, a
full evaluation is performed with the patient off and on medications.  This
evaluation includes the performance of timed motor tasks and stableometry, a
machine which assesses the patients stability and motor responsiveness.
 The pallidotomy must be performed with the patient off medications for at
least 12 hours so that on the evening prior to surgery, Parkinson's
medications are again stopped.  The operation is usually performed in the
morning so that the time off medications is minimized.  All told, the
operation takes 4-5 hours to perform, but there are only 2-3 hours of actual
operating time.
 The first step is to apply the stereotactic frame, a simple procedure which
takes 5 minutes to perform.  This frame is rigidly fixed to the skull at 4
points.  Each site is anesthetized.  The frame is necessary to achieve the
millimeter accuracy we require to perform pallidotomy safely.
 An MRI is then obtained with the frame and the images are transferred to our
computer planning system.  The operation is planned on the computer and the
initial coordinates for the target are selected.  The scalp is then shaved
where the operation is to be performed, and the operation is begun.  Accuracy
is everything; therefore the patient's head is fixed in position for the
operation.  Every effort is made to make the patient as comfortable as
possible.  This includes placement of an air pillow behind the neck, pillows
below the knees, and a nurse who will massage any cramps the patient
experiences.  For those who urinate frequently, a catheter is placed in the
bladder to drain urine during the operation.  It is promptly removed after
surgery.
 The operation is performed through a 1/4 inch incision and a tiny hole that
is drilled through the skull.  The microelectrode is then inserted into the
brain.  Each recording session takes 20-30 minutes to complete.  Typically
only one or two trajectories are required, but sometimes 3 or 4 passes are
needed in order to assure proper placement of the lesion.  During
microelectrode recording, the patient must remain perfectly still and quiet.
 This tends to be the most difficult part of the operation for most patients
and every effort is made to keep them comfortable during this time.
 When recording has revealed our desired trajectory and target point, the
microelectrode is replaced by our lesioning electrode and test stimulation is
performed.  The brain is stimulated with very low voltages to determine our
proximity to critical structures which we want to preserve.  These structures
are the internal capsule and the optic tract.  Damage to the former can cause
paralysis while injury to the latter can cause partial blindness.  The
patient's cooperation during this phase of the operation is critical to the
safety of the procedure.  Our final safety check is to make a "test lesion".
 This is performed by warming the electrode so that the surrounding tissue is
"stunned" but not destroyed.  The patient is then examined, looking for any
new signs of weakness.
 Once all of the safety checks are complete, the lesions are made.
 Typically, 4-5 lesions are made at 2 mm intervals along the lesioning
trajectory.  Each lesion takes 1 minute to perform.  After lesioning, the
electrode is removed and the incision closed with a single suture.  The
stereotactic frame is removed and a head wrap applied.  The patient is then
taken to CT scan to rule out a hemorrhage.  Assuming no hemorrhage occured,
the patient is taken to ICU where he or she will spend the night.  In most
cases, the patient is in ICU by lunch time.  They may eat immediately and
their Parkinson's medications are resumed.
Post-operative Care
 Patients are observed in the ICU overnight for the sake of precaution.  In
most instances, the patient can be discharged home the next day or the day
after.
 Patients return to NYU one week post-op for suture removal and a
post-operative MRI which demonstrates the exact location of the lesion.
 Patients are usually followed by Dr. Fazzini every three months for the
first year.  During this time adjustments may be made in the medications
depending on the patient's changing physiology.  At the anniversary of the
operation each year, we ask patients to return for a day of testing with Dr.
Sterio.

What can you expect?
 The response to pallidotomy is dependent on the patient's symptoms.  A
relief from stiffness is often noted on the operating table while the lesions
are being made.  Dyskinesias secondary to the medication are almost
universally eliminated, something which the patient notices after taking 1 or
2 doses in the ICU.  Family members may note more facial expression.
 There is often an emotional let down in the first week after surgery.  In
hospital, patient's often feel euphoric due to their new found freedoms and
their delight at having survived.  Once the newness of it all has worn off,
there can be a slight let down which is often mistaken for a return of
symptoms.  It is important to keep in mind that there are dramatic
physiologic changes occuring in the patient's brain which take 3-4 months to
complete.  During this time, as is always the case with PD, some days will be
better than others.  Try to keep a long-range perspective and not get
discouraged by 1 or 2 "bad days".  It is our experience that the full effects
of the pallidotomy cannot be assessed until 6 months post-operatively.

Concluding Remarks
 Thanks to many technological advances, modern pallidotomy is much safer and
accurate than the procedure which was performed 35 years ago.  Pallidotomy's
continuing success has provided an invaluable therapeutic option for many PD
patients whose response to medications is waning.  The keys to a successful
pallidotomy are careful patient selection and attention to details while
performing the surgery.  We believe that the excellent results and low
complication rates achieved by the NYU Center for the Study and Treatment of
Movement Disorders speak for themselves.  Our physicians are available for
consultation by appointment.  We can be reached by phone at 212-263-1483.