Forwarded from:  "Robert A. Fink, M.D." <[log in to unmask]>
PALLIDOTOMY FOR PARKINSON'S DISEASE

Seth L. Pullman, M. D., FRCP(C)
Director, Clinical Motor Physiology Laboratory
Movement Disorders Group, College of Physicians and Surgeons
Columbia-Presbyterian Medical Center
New York, NY

Introduction:

>From the 1940s to the mid-1960s, surgical lesions deep in the
movement control centers of the brain were performed to relieve
the symptoms of Parkinson's disease.  Unfortunately, these early
procedures generally met with poor success because localization
of deep brain structures was imprecise, and the operations were
risky.  With the introduction of levodopa in the late 1960s,
most of the symptoms of Parkinson's disease were alleviated
medically.  Medical treatment of Parkinson's disease became the
norm.  Virtually all surgical procedures fell into disuse.
However, by the late 1970s and 1980s, it was found that patients
taking levodopa for more than 5-10 years tended to experience a
loss of benefit from their medications.  Adverse effects such as
dyskinesias and "on-off" fluctuations began to occur.  Interest
in surgical treatment for Parkinson's disease re-emerged.
Furthermore, neurosurgical techniques became safer and the
ability to obtain images of brain structures with CT, MRI, and
PET scans revolutionized the field.  Importantly, accurate
physiological methods of localizing the movement control centers
of the brain were successfully adapted from animal experiments.
These developments have led to new surgical approaches for the
treatment of Parkinson's disease.

Patients must be carefully screened before consideration for
pallidotomy.  Those with the greatest probability of improvement
must be responsive to levodopa but may no longer tolerate side
effects such as levodopa-induced dyskinesias.  Patients cannot
be considered for surgery if they are unresponsive to levodopa.
Clinical features that can be improved by pallidotomy are severe
tremors, "on-off" fluctuations, bradykinesia, and rigidity.
Gait disability is less well treated by pallidotomy.  Patients
should not be demented or depressed, and must be able to
withstand a very long operation.  Patients are awake for most of
the operation, which can last for up to 10 hours with their
heads secured in a metal frame in the operating room.

Before the pallidotomy is performed, a brain MRI is taken and
the metal frame is gently attached to the head.  A CT scan is
then obtained to coordinate anatomic regions with hardware
landmarks.  The patient lies on his or her back with the neck
slightly flexed on the operating table.  Under local anesthetic,
a burr hole is placed in the skull and initial coordinates for
the surgery are made.  A series of metal guide tubes are
positioned such that the electrodes for physiologic recordings
and for surgical lesions can be targeted properly.  Surface skin
electrodes for measuring muscle activity and motion are placed
on the arms and legs to document motor activity.  Under light
anesthesia, several electrode tracks are used to "map"
physiologically the boundaries of the deep brain structures to
be operated on.  Most medical centers performing this
specialized surgery find that electro-physiologic monitoring
prevents potential errors in lesion placement.  In addition,
mild electrical stimulation deep in the brain near the visual
and motor nerve pathways determines the proximity of these
important structures and helps avoid injuring them.

After mapping the deep brain structures, surgical lesioning is
done using a high temperature electrode pin-pointed at the
target.  Multiple lesions are usually placed in two or three
tracks.  Prior to each lesion, low heat testing is used to note
visual changes, motor strength and involuntary movements.
Lesioning with higher heat levels is then done at each site.
Repeated neurologic examinations are performed continuously on
the patient, who remains awake throughout the procedure, and
guides the surgeon by reporting responses to stimulation.

Clinical Results:

Clinical measurements such as the Unified Parkinson's Disease
Rating Scale (UPDRS) and Core Assessment for Intracerebral
Transplantation (CAPIT) are needed for baseline and
post-operative evaluation in both the "on" levodopa and "off"
levodopa states.  Other clinical tests, such as measures of
dyskinesias, speech and cognition are also critical for
post-operative evaluation.  Objective quantification of movement
speed and reaction time with computerized methods is very
important in measuring results of pallidotomy.

Overall, there is 80-100% reduction in dyskinesias after
pallidotomy, allowing patients to maintain pre-operative
levodopa doses without side effects.  Many patients can actually
decrease drug doses and maintain sustained improvement.
However, it is important to note that best "on" motor scores do
not change after pallidotomy.

When "off", patients note improvement in almost all activities
of daily living, and UPDRS "off" motor scores improve by 20-60%.
 Tremor can be markedly reduced but may be variable when
tremor-related activity is not found during intra-operative
physiologic recordings.  Rigidity and bradykinesia improvement
from 10-45% with clear increases in "off" movement speed.
Postural instability, gait and freezing may also show some
improvement.  Combined experience from all centers performing
pallidotomies suggests an overall improvement in "off" scores of
about 30%.

The effect of pallidotomy, particularly on dyskinetic movements,
can be striking and immediate.  Patients should be cautioned,
however, not to expect "miracles" as the popular press has
reported.  Long term effects are still being evaluated, but it
appears that many patients have shown continued improvement for
well over two to three years.

Complications:

Because general anesthesia is not used, complications related to
this technique do not occur in pallidotomy.  However, there is a
less than one percent risk of serious intra- or post-operative
hemorrhage, infection, or death.  Because the deep brain regions
to be lesioned are adjacent to visual and motor areas in the
brain, there is a three to six percent risk of partial blindness
or paralysis.

Adverse psychological changes such as decreased short term
memory, depression and word finding difficulties have occurred
in patients after pallidotomy, usually in those with
pre-existing symptoms.  These complications are more likely to
occur when the pallidotomy is done on the left side.  Bilateral
pallidotomy lesions may result in even greater speech and
psychological changes.

Other Surgical Procedures for Parkinsonism:

Other surgical procedures of potential use in patients with
Parkinson's disease include lesioning other deep brain
structures (such as thalamotomy), implantation of high frequency
electronic stimulators, and neural grafting with transplanted
cells.  Thalamotomies are highly effective in reducing severe
tremors, but are not effective with other symptoms of
Parkinson's disease or drug-related dyskinesias.  Implanted
stimulators hold significant promise but that technique has not
been performed enough to make critical assessments at this time.
 Stimulators have the potential advantage of being able to be
turned on and off, but may not treat as large an area of the
brain as pallidotomy.  Transplantation of fetal grafts into deep
brain structures theoretically can be used to replace dopamine
loss in Parkinson's disease.  Studies are ongoing but clinical
effects from transplantation may require at least a year to
become evident, and not enough data from patients has been
collected to judge the results.

Conclusion:

Pallidotomy is a relatively safe and effective treatment for
carefully screened patients with Parkinson's disease who have
levodopa-induced dyskinesias, "on-off" fluctuations, tremors and
bradykinesia.  Overall, symptoms improve by about 30% with
sustained improvement potentially for over two to three years.
Gait abnormalities and freezing show less consistent
improvement, and peak "on" scores do not improve.  Pallidotomies
probably should not be performed on patients with significant
cognitive impairment and bilateral pallidotomies should be
approached with caution due to potential speech and
psychological problems.

 ===========================================================================
Barbara Patterson                               [log in to unmask]
HSC 2J22                                        905-525-9140, ext. 22403
                        School of Nursing
 ===========================================================================