Address for Correspondence:
N. Eskandar, M.D.
Massachusetts General Hospital
15 Parkman St. ACC # 331
Boston, MA 02114
Patient Appointments: 617.724.6590
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Treatment of Parkinson's disease.
Department of Neurology, University of California, San Francisco,
School of Medicine 94143-0114.
West J Med (UNITED STATES) Sep 1994, 161 (3) p303-8
Pharmacotherapy with levodopa for
Parkinson's disease provides symptomatic benefit, but fluctuations
in (or loss of) response may eventually occur. Dopamine agonists
are also helpful and, when taken with low doses of levodopa, often
provide sustained benefit with fewer side effects; novel agonists
and new methods for their administration are therefore under study.
Other therapeutic strategies are being explored, including the use
of type B monoamine oxidase inhibitors to reduce the metabolic breakdown
of dopamine, catechol-O-methyltransferase inhibitors to retard the
breakdown of levodopa, norepinephrine precursors to compensate for
deficiency of this neurotransmitter, glutamate antagonists to counteract
the effects of the subthalamic nucleus, and various neurotrophic
factors to influence dopaminergic nigrostriatal cells. Surgical
procedures involving pallidotomy are sometimes helpful. Those involving
cerebral transplantation of adrenal medullary or fetal mesencephalic
tissue have yielded mixed results; benefits may relate to the presence
of growth factors in the transplanted tissue. The transplantation
of genetically engineered cell lines will probably become the optimal
transplantation procedure. The cause of Parkinson's disease may
relate to oxidant stress and the generation of free radicals. It
is not clear whether treatment with selegiline hydrochloride (a
type B monoamine oxidase inhibitor) delays the progression of Parkinson's
disease, because the drug also exerts a mild symptomatic effect.
Daily treatment with vitamin E (a scavenger of free radicals) does
not influence disease progression, perhaps because of limited penetration
into the brain. (57 Refs.)
Klockgether T; Loschmann PA; Wullner U
New medical and surgical treatments for Parkinson's disease.
University of Tubingen, Germany.
Curr Opin Neurol (UNITED STATES) Aug 1994, 7 (4) p346-52,
This article reviews new medical and
surgical treatments for Parkinson's disease (PD). Catechol-O-methyl-transferase
(COMT) inhibitors supplement the variety of antiparkinsonian drugs
interacting with the dopaminergic system. Clinical studies show
that COMT inhibitors prolong the action of levodopa in patients
with the "wearing off" phenomenon. The atypical antipsychotic
drug clozapine is the treatment of choice for the alleviation of
levodopa-induced psychosis. Clozapine also has beneficial effects
on tremor and levodopa-induced dyskinesias. Thus, COMT inhibitors
and clozapine provide new opportunities for the treatment of patients
with longstanding PD and fluctuating responses to levodopa. Experimental
evidence in animals suggests that glutamate antagonists have symptomatic
and neuroprotective actions in PD. At present, however, only weak
antiglutamatergic drugs that have low specificity, such as memantine,
amantadine, and budipine are available for clinical studies. Neurotrophic
factors, in particular ciliary neurotrophic factor and glial cell
line-derived neurotrophic factor, are among the most promising new
approaches for neuroprotection in PD. Problems of bioavailability,
however, thus far preclude their use in patients. An improved understanding
of the pathophysiology of parkinsonism has led to a renaissance
of stereotaxic surgery. The subthalamic nucleus is a potential new
target for surgical intervention. Ventroposterior pallidotomy has
been shown to improve not only rigidity and tremor, but also akinesia.
The techniques for thalamic interventions have been refined by introducing
chronic thalamic stimulation. Future transplantation approaches
to PD will focus on the use of genetically modified cells carrying
genes for dopamine-synthesizing enzymes or neurotrophic factors.
Animal studies show the feasibility of in vivo gene transfer for
the treatment of PD. (53 Refs.)
Iacono RP; Lonser RR; Mandybur G; Morenski JD; Yamada S; Shima F
Stereotactic pallidotomy results for Parkinson's exceed those of
Division of Neurosurgery, Loma Linda University Medical Center,
Am Surg (UNITED STATES) Oct 1994, 60 (10) p777-82
Fetal graft research and renewed interest
in Leksell's postero-ventral pallidotomy (PVP) stimulated reconsideration
of surgical therapy for Parkinson's disease (PD), particularly with
regard to improving akinetic symptoms previously thought resistant
to surgical lesions. Review of our series and other published results
of PVP and fetal graft show that PVP has beneficial effects on both
akinetic and hyperkinetic symptoms that better the results reported
for fetal graft implantation and other conventional stereotactics.
Presented are the results of 60 consecutive patients, 55 of whom
underwent PVP, and 5 who underwent fetal graft implantation. Using
the Unified Parkinson's Disease Rating Scale (UPDRS), we found that
PVP gave significant (P < 0.05) reductions in akinetic symptomatology
including freezing, arising from a chair, posture, gait, postural
instability, and bradykinesia. Fetal graft patients had significant
reductions in two akinetic symptoms: bradykinesia and postural instability.
PVP's dramatic therapeutic effects on akinesia may be explained
by interruption of amplified collateral inhibitory output from the
pallidum to brain stem locomotor centers such as the pedunculopontine
nucleus, whereas interruption of collaterals to ventral lateral
thalamus by PVP may account for the elimination of hyperkinesia.
The excellent results of PVP represent a significant advance in
the surgical treatment of PD. (33 Refs.)
Rand RW; Jacques DB; Melbye RW; Copcutt BG; Fisher MR; Levenick
Gamma Knife thalamotomy and pallidotomy in patients with movement
disorders: preliminary results.
Neurosciences Institute, Hospital of the Good Samaritan, Los Angeles,
Stereotact Funct Neurosurg (SWITZERLAND) 1993, 61 Suppl 1 p65-92
The Leksell Gamma Knife is a useful
and safe method to perform thalamotomy and pallidotomy in selected
older patients with Parkinson's disease and related movement disorders.
In this preliminary report, 2 of 3 patients with severe intention
tremor were relieved of their symptoms by thalamotomy, as were 4
of 7 patients with Parkinson's tremor. Four of 8 patients had significant
improvement of contralateral rigidity following pallidotomy.
Iacono RP; Lonser RR
Reversal of Parkinson's akinesia by pallidotomy [letter]
Lancet (ENGLAND) Feb 12 1994, 343 (8894) p418-9,
[Surgical treatment of Parkinson's disease] In Japanese
Department of Neurological Surgery, Wakayama Medical College.
Nippon Rinsho (JAPAN) Nov 1993, 51 (11) p2940-6
Surgical treatment for Parkinson's
disease began by blocking of the pyramidal system in early part
of this era. In 1942, Meyers performed Ansotomy for the treatment
of Parkinsonism without leaving hemiplegia, leading subsequent operating
target to blocking of pallidofugal fiber. Then, the development
of stereotaxy in 1947 caused an operative progress to Pallidotomy
and further to Thalamotomy. Although the spread of levodopa therapy
gradually brought about decline of surgical treatment, Thalamotomy
became to be reexamined in view of not a little problems about and
side effects of levodopa therapy. With the development of CT, MRI
and the like, Thalamotomy via MRI-stereotaxy was developed, making
operations safer and surer. Besides, transplantation of dopamine
neurons into the striatum was tried as an essential treatment and
is in clinical application via animal experiments. Fetal ventral
mesencephalic tissue and adrenal medullary tissue are available
therefore, but demerits are such that the former poses some ethical
problem and the latter is poor and short-lived response. The transplantation
of stellate ganglion into the striatum, which we have recently developed
is safe and more effective than the adrenal medullary tissue. The
respective one thirds of the cases did without levodopa following
transplantation, needed half as much as the preoperative levodopa
dose and needed the same as the latter. Although Horner's syndrome
was noted in all cases following transplantation, no Parkinson syndrome
became aggravated in any one of the cases. (15 Refs.)
Widner H; Rehncrona S
Transplantation and surgical treatment of parkinsonian syndromes.
Department of Neurology, University Hospital, Lund, Sweden.
Curr Opin Neurol Neurosurg (UNITED STATES) Jun 1993, 6 (3) p344-9
Neurosurgical attempts to correct
parkinsonism use strategies aimed either at alleviating the underlying
dopamine deficiency or at correcting abnormal compensatory effects
in neural circuits within the basal ganglia. During the review period,
clinical trials of four different neurosurgical approaches were
reported. These approaches are intracerebral transplantation of
fetal dopamine neurons, intracerebral transplantation of adrenal
medullary tissue, tremor-reducing surgical lesions in the ventrolateral
thalamus, and ventroposterior pallidotomy aimed at reducing akinesia
and rigidity. Experimental studies in rats and monkeys designed
to explore mechanisms of graft actions were also reported. (33 Refs.)
Goetz CG; De Long MR; Penn RD; Bakay RA
Neurosurgical horizons in Parkinson's disease.
Department of Neurological Sciences, Rush-Presbyterian-St. Luke's
Medical Center, Chicago, IL 60612.
Neurology (UNITED STATES) Jan 1993, 43 (1) p1-7
Based on recent neuroanatomic and
physiologic discoveries, neurosurgical therapies may increasingly
complement and extend pharmacologic management of Parkinson's disease.
Procedures showing promise include subthalamotomy and pallidotomy;
thalamic electrical stimulation may also offer application for tremor
control. Transplantation of adrenal chromaffin cells has not been
associated with consistent long-term improvement in most patients,
and fetal mesencephalic transplantation remains controversial. Trophic
factors that may be pivotal to cellular repair and survival of transplanted
tissue have potential therapeutic roles when purified and perfused
centrally or when the cells that produce the factors are transplanted.
Laitinen LV; Bergenheim AT; Hariz MI
Ventroposterolateral pallidotomy can abolish all parkinsonian symptoms.
Department of Neurosurgery, Sophiahemmet Hospital, Stockholm, Sweden.
Stereotact Funct Neurosurg (SWITZERLAND) 1992, 58 (1-4) p14-21
pallidotomy in 46 parkinsonian patients resulted in a complete or
almost complete and long-lasting relief of rigidity and hypokinesia
in 91% of the patients. Good tremor effect was obtained in 80% of
them. The L-dopa-induced dyskinesias, gait and speech improved in
most patients. Complications were observed in 7 cases after 51 pallidotomies,
i.e. 14% (partial homonymous hemianopia in 6 and transient dysphasia
and facial weakness in 1). We believe that the good effect of surgery
is based on interruption of some striopallidal or subthalamopallidal
Taira T; Kawamura H; Tanikawa T; Iseki H; Amano K
Unexpected movement disorders in neurosurgical practice: report
of three cases.
Department of Neurosurgery, Tokyo Women's Medical College, Japan.
Surg Neurol (UNITED STATES) Aug 1992, 38 (2) p135-40
Hyperkinetic movement disorders may
develop as a complication of stereotactic thalamotomy or pallidotomy.
However, such movement disorders are uncommon after nonsterotactic
intracranial operations. The authors report three cases of involuntary
movement disorders unexpectedly developing after intracranial operations.
The patients had undergone clipping of an internal carotid aneurysm,
removal of an intracerebral hematoma, and resection of a tentorial
meningioma. Two patients developed choreic movements and a dystonic
posture of the unilateral upper extremity. One patient showed a
tremor that had features of both parkinsonism and essential tremor.
The symptoms of these patients were medically uncontrollable, and
they were successfully treated with stereotactic ventrolateral thalamotomy.
Laitinen LV; Bergenheim AT; Hariz MI
Leksell's posteroventral pallidotomy in the treatment of Parkinson's
disease [see comments].
Department of Neurosurgery, Sophiahemmet Hospital, Stockholm, Sweden.
J Neurosurg (UNITED STATES) Jan 1992, 76 (1) p53-61
Between 1985 and 1990, the authors
performed stereotactic posteroventral pallidotomies on 38 patients
with Parkinson's disease whose main complaint was hypokinesia. Upon
re-examination 2 to 71 months after surgery (mean 28 months), complete
or almost complete relief of rigidity and hypokinesia was observed
in 92% of the patients. Of the 32 patients who before surgery also
suffered from tremor, 26 (81%) had complete or almost complete relief
of tremor. The L-dopa-induced dyskinesias and muscle pain had greatly
improved or disappeared in most patients, and gait and speech volume
also showed remarkable improvement. Complications were observed
in seven patients: six had a permanent partial homonymous hemianopsia
(one also had transient dysphasia and facial weakness) and one developed
transitory hemiparesis 1 week after pallidotomy. The results presented
here confirm the 1960 findings of Svennilson, et al., that parkinsonian
tremor, rigidity, and hypokinesia can be effectively abolished by
posteroventral pallidotomy, an approach developed in 1956 and 1957
by Lars Leksell. The positive effect of posteroventral pallidotomy
is believed to be based on the interruption of some striopallidal
or subthalamopallidal pathways, which results in disinhibition of
medial pallidal activity necessary for movement control.
Correlation between clinical outcome and size and site of the lesion
in computed tomography guided thalamotomy and pallidotomy.
Department of Neurosurgery, University Hospital, Ume.ANG.a, Sweden.
Stereotact Funct Neurosurg (SWITZERLAND) 1990, 54-55 p172-85
Fourteen thalamotomies and five pallidotomies
were performed in 19 patients with hereditary intention tremor or
Parkinson's disease. The target coordinates were determined by a
stereotactic computed tomography study using the Laitinen noninvasive
stereoadapter. Surgery was done without ventriculography. The patients
were assessed 3-12 months later. In a postoperative stereotactic
computed tomography study, the positions of the thalamic and pallidal
targets were marked, and the coordinates of the center of the lesion
were measured in relation to these targets. The volume of the lesion
was calculated. In 3 thalamic lesion patients, no lesion could be
visualized. The size of the eleven visible thalamic lesions ranged
from 4 to 75 mm3 (mean 26), and the size of the 5 pallidal lesions
ranged from 28 to 150 mm3 (mean 67). On the average, the center
of the lesion was 1.4 mm medial to the position of the anatomical
target (p less than 0.002). Neither size nor site of the lesion
correlated with the clinical outcome.
Stereotactic pallidotomy in extrapyramidal disorders.
Appl Neurophysiol (SWITZERLAND) 1985, 48 (1-6) p283-7
The results of stereotactic pallidotomy
in 37 patients with extrapyramidal disorders are presented. All
patients had the same RF lesions and target coordinates. The patients
are classified into 5 groups according to the clinical picture.
These results are compared with those obtained by thalamotomy in
a similar group of patients. The main indications for pallidotomy
are given. The spatial representation of globus pallidus medialis
according to Andrews and Watkins, Talairach and the author are shown
and their differences discussed.