The Neurosciences Institute, which is associated with Good Samaritan
Hospital in Los Angeles, sponsored a symposium on Nov. 2-3, 1996
in Rancho Mirage, CA. Dr. Chance made her presentation there.

I thank Carole Hilton for making this information available to the
Parkinsn archives.

Clinical follow-up of Post-Pallidotomy and Neurotransplantation
Patients

- Dr. Janet Chance

        The treatment of Parkinson's disease is continuing to change.
Initially there was little to offer, but surgery and ablative
techniques were performed for severe tremor and rigidity.   The
development of L-Dopa revolutionized the management of Parkinson's
disease and surgery fell into disuse.  The next great breakthrough
was the development of an animal model (MPP+ induced) and we are
now seeing results from this with the development of more selective
Dopamine agonists and the COMT inhibitors.  However, none of the
drugs currently available have any significant effect on the
disease process.   Consequently, as the patients progress they
require more complex drug regimens and medication side effects,
especially the long term side effects of L-Dopa, may become
intolerable to both patient and care giver.

        For a number of patients, currently a small and highly
selective group, surgical treatment has again become an
alternative.   With the advent of microsurgical techniques,  a
clearer understanding of the anatomic microstructure and patho-
physiologic function of the basal ganglia, the lesions can be made
with far greater precision. Stereotactic radio frequency oblation,
electrophysiologic stimulation and computer integration of MR
images with stereotactic frames have minimized morbidity.  Current
procedures  available  include  thalamotomy and VIM stimulation
(primarily for tremors), medial pallidotomy and neural grafting.
It is with the latter two procedures, or rather the post operative
management, that I wish to deal.

        Studies of basal ganglia connections have shown that output
from the striatum to GPi occurs over two pathways, the direct and
the indirect.  The direct pathway inhibits GPi.  The indirect
pathway by disinhibition of excitatory subthalimopallidal neurons
stimulates GPi.  Lack of dopamine ultimately results in decreased
activity in the direct pathway and increased activity in the
indirect pathway, resulting in excessive inhibition of thalamo
cortical neurons.  Based on this, pallidotomy should improve the
symptoms of Parkinson's disease.   Results, however, have been
somewhat mixed.  The most dramatic effect is the profound reduction
in L dopa induced dyskinesia contralateral to the lesion.  A degree
of ipsilateral improvement is also seen.

        I will discuss follow up in five patients who had unilateral
or bilateral pallidotomy.  In summary, all patients had cessation
or near complete cessation of dyskinesia contralateral to the
lesion with a moderate decrease in ipsilateral dyskinesia.  Two of
five patients had a moderate decrease in rigidity.  There was no
significant functional improvement in bradykinesia, although rapid
successive movements did increase in amplitude.    Speech and
postural reflexes were unchanged in all patients.  Gait improved in
that the severe dyskinesias ceased.

        There was no significant decrease in Sinemet requirements in
any patient, but it was significantly better tolerated.  It was
possible to decrease by 25 to 30 percent the requirement for
Dopamine agonists, Amantidine and anticholinergics.  Four of five
patients were extremely satisfied with their outcome, citing the
reduction of dyskinesia as the most pleasing aspect.  Perioperative
morbidity consisted of transient left facial weakness in patient
number two.  Patient number four was briefly hospitalized three
weeks post operatively with what was initially thought to be stroke
but turned out to be exhaustion.  He had been playing on the beach
all day with his grandchildren and staying up until the small hours
of the morning with his children.  MR during his admission appeared
to show subacute damage to the left pallidum and the patient had
had a right pallidotomy.    Approximately  three  months  post
operatively patient number three developed apraxia of eye opening.
It is not clear that this is directly connected to the surgery, but
the patient had a good response to Baclofen.

        Follow up in these patients ranges from three months to three
years and four of the five patients remain very satisfied.  Disease
progression was not affected and the patients did not have a
decrease in their Sinemet requirements, but found that they
tolerated it much better.  it has been possible to increase the
dosage without significant side effects.

        Bilateral fetal implants were performed on three patients,
each receiving four to six donors per side.  In contrast to the
pallidotomy subjects, two of the three patients had a very stormy
course for the first six months post operatively.

        Initially there was a significant increase in symptoms with
marked bradykinesia, tremor, unpredictable freezing and an increase
in "off" time.  In addition to this, patient number three developed
hiccup and confusion, which cleared within one month.

        By 2-1/2 months post implant, patients one and three developed
major depressive episodes, with anxiety, rumination, hopelessness
and anhedonia.  Both patients required psychiatric intervention.
During this period both patients felt they were making no progress
despite clinical evidence to the contrary.  In month six both
patients improved, almost overnight, with cessation of depression,
optimism and resumption of previously pleasurable activities.

        From month two on, motor function was slowly improving in all
patients, although need for Sinemet did not decrease significantly.
There was an improvement in "on" time and less unpredictable
freezing.

        At month nine, patient two, her pre-operative status with a
slightly lower dose of Sinemet, resumed living alone.   Patient
three had a significant decrease in "off" time and was able to
spend considerable time on his computer and ham radio.  At one year
post implant patient two continued to feel well.  Patient one had
returned to work and patient three was doing well with reduction in
tremor compared to preoperative status, and with a decrease in
"off" time.   He was somewhat discouraged in that his Sinemet
requirement was unchanged from preoperatively.

        During the first year post implant all patients - especially
one and three - needed a considerable amount of care.  Phone calls
from them or their families were frequent, sometimes daily, and
office visits were also increased in number.  This was maximal in
the first six months.   It became evident that peer support was
necessary and was found to be extremely helpful by the patients
involved.   We have established an informal "buddy" system for
future neural transplant patients and their families which will
start preoperatively.

        The initial worsening in these patients was likely due to a
combination of the mechanical effects of the implant placement,
together with edema.  The depression is more difficult to explain.
The Yale Group did not find a clear relationship between depression
and neural transplant.  However, neither of my patients had any
prior history of psychiatric illness and in both patients the
improvement was abrupt and quite striking, occurring at six months
post implant.  They both saw the same psychiatrist, who was also
impressed by the similarity between them.

        In  summary,  both procedures  are useful  in a  small  and
carefully selected group of patients.  Pallidotomy is particularly
helpful for dyskinesias, the patients tolerate the procedure well,
and post operative management is simple.  Neural transplant is more
problematic.  Peer support is essential, best managed on a "buddy"
system starting preoperatively and involving the care giver as
well.  Depression does appear to be a significant problem and this
merits further exploration.   However,  it also appears to be
relatively self-limited, clearing within six months.


BIBLIOGRAPHY

1.      Neurosurgical Horizons in Parkinsons Disease; Goetz, C.G., et
al.  Neurology 1993; 43:l-7

2.      The Role of Surgery in Parkinsons Disease Management Olanow,
C.W.; Marsden, C.D; Lang, A.E.; Goetz, C.G.  Neurology 1994;
44 (suppl. 1): S17-S20

3.      Ventroposterolateral Pallidotomy Laitinen, L.V. - Stereotact
Functional Neurosurgery 1994; 62:41-52

4.      Pallidotomy for Parkinsons Disease  Laitinen, L.V.   -
Neurosurgical Clinics of North America 1995; 6:105-112

5.      Sterotactic Ventral Pallidotomy for Parkinsons Disease
Dogali, M., et al - Neurology 1995; 45:753-761

6.      Efforts of Posteroventral Pallidotomy on Parkinsons Disease
Dogali, M., et al - Advances in Neurology 1996; 69:585-590

7.      Effects of GPi Pallidotomy on Motor Function in Parkinsons
Disease Lozano, A.M., et al - Lancet 1995; 346:1383-1387

8.      Unilateral Transplantation of Human Fetal Mesencephalic Tissue
Into the Camdate Nucleus of Patients with Parkinsons Disease
Spencer, D.D., et al - NEJM 1992; 327:1541-1548

9.      Survival of Implanted Fetal Dopamine Cells and Neurologic
Improvement 12-46 Months After Transplantation for Parkinsons
Disease Firod, C.R., et al - NRJM 1992; 327:1541-1555

10.      Eighteen Month Course of Two Patients with Grafts of Fetal
Dopamine Neurons for Severe parkinsons Disease Hoffer, B.J.,
et al - Experimental Neurology 1992; 118:243-252

11.      Bilateral Fetal Nigral Transplantation into the Post
Commissural Putamen in Parkinsons Disease Freeman, T.B., et al
- Annals of Neurology 1995; 38:379-388

12.      Psychiatric Status After Human Fetal Mesencephalic Tissue
Transplantation in Parkinsons Disease Price, L.H., et al -
biol. Psychiatry 1995; 38:498-505

13.      General Cognitive Ability Following Unilateral and Bilateral
Ventgral Mesencephalic Tissue Transplantation for Treatment of
Parkinsons Disease Sass, K.J., et al - Arch. Neurology 1995;
52:680-686

[log in to unmask]      That man may last, but never lives,
                        Who much receives, but nothing gives;
HomeBoy #Parkinsons         Whom none can love, whom none can thank,--
                               Creation's blot, creation's blank.
John Cottingham           Thomas Gibbons (1720-1785): When Jesus dwelt.