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Parkinsn Current Topics
TITLE: Serotonergic decompensation in the akinetic
expression of Parkinson's disease.
AUTHORS: Iacono RP; Nahab FB; Nahab FH
AUTHOR AFFILIATION: Loma Linda University School of Medicine,
Department of Surgery, USA.
SOURCE: Int J Neurosci 2000;101(1-4):57-63
CITATION IDS: PMID: 10765990 UI: 20227057
ABSTRACT: The current diagnostic and treatment paradigm for the
akinetic form of Parkinson's disease asserts that the majority of
symptoms and treatment phenomena arise from a dysfunctional
dopaminergic system. Recent studies have attempted to determine
the roles of other biogenic amine neurotransmitters such as
serotonin and norepinephrine. Metabolic breakdown product studies
of Parkinsonian and non-Parkinsonian cerebrospinal fluid (CSF)
samples indicate significant differences in the levels of
serotonin and norepinephrine in addition to the levels of
dopamine. Such changes may suggest that current pharmacologic
therapies that attempt to restore only dopamine are inadequate,
and require accompanying therapies to elevate serotonin and
norepinephrine levels.
2000/07
2000/15 11:00
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TITLE: Electrophysiological versus image-based targeting
in the posteroventral pallidotomy.
AUTHORS: Carlson JD; Iacono RP
AUTHOR AFFILIATION: School of Medicine and Department of
Physiology and Pharmacology, Loma Linda University, California,
USA. carljon@sc.llu.edu
SOURCE: Comput Aided Surg 1999;4(2):93-100
CITATION IDS: PMID: 10494139 UI: 99425402
ABSTRACT: OBJECTIVE: To study the functional accuracy of
stereotactic targeting for the posteroventral pallidotomy (PVP),
comparing targets chosen on magnetic resonance images (MRI), and
fused MRI to computed tomographic (CT) images, with
electrophysiologically refined anatomical targets.
METHDOS AND MATERIALS: For each of the 10 pallidotomies three sets of targets were collected, beginning with the MRI targets. The second target set was measured on images generated by nonlinear volumetric fusion of MRI images with CT using Image Fusion (Radionics, Inc.). The anatomical target site was then determined electrophysiologically with intraoperative microelectrode recording and macroelectrode stimulation guidance.
RESULTS: Magnetic resonance imaging or MRI-CT fused images alone would not have been sufficiently accurate to preclude visual or motor complications in the posteroventral pallidotomy, based on our target located within 1 mm of the optic tract and within 2 mm of the internal capsule. In 2 of the 10 cases of either MRI or fused images, the targets were dangerously close to the optic tract. Two of 10 of the fused targets were within the internal capsule. The fusion of MRI with CT did not functionally improve the targeting accuracy of MRI, since the means of the MRI targets and the fused targets were statistically the same. Individually, however, the MRI target was different from the fused target in each case by an average radial distance of 3.5 +/- 2.3 mm, but such corrections were not statistically or surgically significant.
CONCLUSIONS: Image-based targeting including MRI or fused
MRI-CT data may not be sufficiently accurate to prevent capsular
or visual deficits in the posteroventral pallidotomy,
necessitating electrophysiological refinement. In this report,
the functional accuracy of MRI was not improved by fusion with
CT. Copyright 1999 Wiley-Liss, Inc.
1999/09
1999/24 09:00
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TITLE: A comparative study on neurochemistry of
cerebrospinal fluid in advanced Parkinson's disease.
AUTHORS: Liu H; Iacono RP; Schoonenberg T; Kuniyoshi S; Buchholz
J
AUTHOR AFFILIATION: Department of Pharmacology/Physiology, Loma
Linda University Medical School, California 92350, USA.
SOURCE: Neurobiol Dis 1999 Feb;6(1):35-42
CITATION IDS: PMID: 10078971 UI: 99176857
ABSTRACT: This study addresses two issues: (1) the comparative
neurochemistry of classic tremor type of Parkinson's disease or
PD-A and akinetic type of Parkinson's disease or PD-B; and (2)
the neurochemistry of levodopa failure syndrome (LDFS).
Cerebrospinal fluid from the lateral ventricle was collected from
50 patients with idiopathic Parkinson's disease of PD-A and PD-B.
Levels of monoamine neurotransmitters and metabolites were
determined using high performance liquid chromatography. We have
found that (1) 5-hydroxylindoleacetic acid (5-HIAA) level is
significantly lower in PD-B than in PD-A; (2) 5-HIAA level is
inversely associated with score of part one of United Parkinson's
Disease Rating Score (UPDRS); (3) 5-HIAA level is inversely
associated with score of part four of UPDRS; (4) 3-O-methyldopa
(3-OMD) level is positively associated with levodopa failure
syndrome (LDFS) assessed by part four of UPDRS and inversely
associates with 5-HIAA. From these data, it can be inferred that
serotonergic activity is decreased in PD-B to a greater extent
than in PD-A and that decreased serotonergic activity plays a
role in LDFS.
1999/03
1999/17 03:05
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TITLE: Concentrations of indoleamine metabolic
intermediates in the ventricular cerebrospinal fluid of advanced
Parkinson's patients with severe postural instability and gait
disorders.
AUTHORS: Iacono RP; Kuniyoshi SM; Ahlman JR; Zimmerman GJ; Maeda
G; Pearlstein RD
AUTHOR AFFILIATION: Clinical Neuroscience Research Group, Loma
Linda University, Loma Linda Medical Center, CA 92350, U.S.A.
SOURCE: J Neural Transm 1997;104(4-5):451-9
CITATION IDS: PMID: 9295177 UI: 97439621
ABSTRACT: Postural instability and gait disorders (PIGD) are the
primary causes of disability in many but not all advanced
Parkinson's disease (PD) patients. We have measured the
concentrations of serotonin, 5-hydroxytryptophan (5-HTP),
5-hydroxy-3-indoleacetic acid (5-HIAA), and homovanillic acid
(HVA) in samples of ventricular cerebrospinal fluid from ten PD
patients with severe disability from PIGD and from ten PD
patients with tremor and levodopa induced dyskinesia as their
predominant motor dysfunction. The two groups were prospectively
matched for duration of disease and age. No significant
differences between the two groups were found in the
concentration (mean +/- SD in ng/ml, PIGD dominant vs.
tremor-dyskinesia dominant) of 5-HIAA (106 +/- 50 vs. 99 +/- 34)
or HVA (1,068 +/- 595 vs. 881 +/- 469). Serotonin concentration
was significantly lower (0.7 +/- 0.5 vs. 1.5 +/- 0.9) and 5-HTP
concentration was substantially higher (684 +/- 1,054 vs. 6 +/-
5) in the patient group with PIGD as their predominant symptoms.
Thus, the distinguishing feature of patients with severe PIGD
appears to be a derangement in indoleamine metabolism at the
reaction step catalyzed by aromatic amino acid decarboxylase
(AADC). These findings suggest that aggravation of PIGD in
advanced Parkinson's may be related in part to impaired
serotonergic transmission secondary to inhibition or down
regulation of AADC.
1997/09
1997/19 00:00
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TITLE: Gamma knife pallidotomy: case report.
AUTHORS: Bonnen JG; Iacono RP; Lulu B; Mohamed AS; Gonzalez A;
Schoonenberg T
AUTHOR AFFILIATION: Division of Neurosurgery, University of Texas
Medical Branch, Galveston, USA.
SOURCE: Acta Neurochir (Wien) 1997;139(5):442-5
CITATION IDS: PMID: 9204114 UI: 97348047
ABSTRACT: We report a case of gamma knife pallidotomy resulting
in a permanent contralateral homonymous hemianopsia and transient
contralateral hemiparesis with some improvement in contralateral
parkinsonian symptoms. This case illustrates the risk of gamma
knife pallidotomy which precludes physiologic target localization
and can subject structures surrounding the target to a
significant radiosurgical dose. Until noninvasive physiologic
target localization is available gamma knife pallidotomy and
thalamotomy should be limited to patients with an unacceptably
high risk for stereotactic percutaneous thermocoagulation.
1997/01
1997/01 00:00
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TITLE: Electrophysiologic target localization in
posteroventral pallidotomy.
AUTHORS: Iacono RP; Carlson JD; Kuniyoshi SM; Li YJ; Mohamed AS;
Maeda G
AUTHOR AFFILIATION: Loma Linda University Medical Center, CA,
USA.
SOURCE: Acta Neurochir (Wien) 1997;139(5):433-41
CITATION IDS: PMID: 9204113 UI: 97348046
ABSTRACT: The current interest in stereotactic posteroventral
pallidotomy (PVP) for treating Parkinson's disease and the
variability of published results have raised questions regarding
techniques for target localization. In our technique the probe is
guided to the optimum target at the most ventral pallidum and
ansa lenticularis by macroelectrode stimulation of the internal
capsule and optic tract from within the globus pallidus, with the
thresholds providing a relative measure of the electrode
proximity to these structures. We have characterized these
localizing macroelectrode stimulation parameters in 57
posteroventral pallidotomies with consistent anatomic lesion
placement, excellent outcome, and no complications. Using a 1.8 x
2.0 mm radiofrequency electrode for macroelectrode stimulation
(RFG-3C, Radionics Inc.), minimum voltages (thresholds) to
activate motor (at a frequency of 2 Hz) or visual (at a frequency
of 100 Hz) responses as well as impedance measurements were
obtained at the final target (Tf) and at distances proximal to Tf
along the electrode trajectory. The visual and motor threshold
voltages at Tf via our standard approach angles (50 degrees above
base plane, 20 degrees from the sagittal plane), had a range of
1.0 to 1.5 V, and 2.0 to 3.5 V respectively. We also found that
as the probe approaches Tf there is a significant decrease in
voltage thresholds for motor (P < .0001) and visual (P <
.0001) responses in an individual patient indicating that the
probe is converging on these structures. Increases in impedance
between Tf, 2-3 mm, and 4-5 mm proximal to Tf were also
statistically significant (P < .0001). Microelectrode
recording to electrophysiological neuronal activity at various
points along the trajectory towards the target showed distinct
firing patterns providing identification of the globus pallidus
externus and internus, ansa lenticularis, and optic tract.
Macroelectrode electrophysiological stimulation within the target
volume, inducing threshold responses in the internal capsule and
optic tract, provides for accurate localization of the most
effective PVP target in the ansa lenticularis. In unresponsive
patients, the utilization of microelectrode recording for the
identification of the pallidal borders and the optic tract
improves safety.
1997/01
1997/01 00:00
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TITLE: Normalization of middle latency auditory P1
potential following posterior ansa-pallidotomy in idiopathic
Parkinson's disease.
AUTHORS: Mohamed AS; Iacono RP; Yamada S
AUTHOR AFFILIATION: Department of Neurosurgery, Loma Linda
University Medical Center, CA 92350, USA.
SOURCE: Neurol Res 1996 Dec;18(6):516-20
CITATION IDS: PMID: 8985952 UI: 97138980
ABSTRACT: The P1 potential (50 msec) of middle latency auditory
evoked potential was evaluated in seven patients with advanced
idiopathic Parkinson's disease before and after contemporaneous
bilateral posterior ansa-pallidotomy. P1 potential was lacking in
two patients preoperatively and was prolonged in the remainder of
the patients when examined in a best medicated 'on' state. All
patients showed varying degrees of dementia preoperatively on
clinical examination. Remarkable improvement in their Unified
Parkinson's Disease Rating Scale (UPDRS) scores during 'on'
states from a mean of 45.85 to 14.28 post-operatively was
achieved. Subsidence of akinetic symptoms, abolishment of
dyskinesia, improvement in gait freezing, rigidity, and tremors
represented main areas of improvement. P1 latencies and
amplitudes reverted back to normal values in six patients
including the two patients who lacked P1 wave preoperatively. One
patient showed mild worsening of both Pa and P1 values
post-operatively attributed to sleepiness during testing, a
transient phenomenon commonly encountered following posterior
ansa-pallidotomy. The post-operative P1 changes were
statistically significant for both latencies and amplitudes at p
= 0.078 and p = 0.073, respectively, for all seven patients using
one tailed paired t-test. The change in UPDRS post-operatively
best correlated with the post-operative difference in P1;
specifically, UPDRS subscore II with P1 amplitude (r = -0.068, p
= 0.09), and UPDRS subscore IV with Pa: P1 ratio (r = +0.77, p =
0.04). Earlier clinical and experimental work support the
tegmental pedunculopontine nucleus (PPN) as the site of origin of
P1 wave. In addition, its presence reflects the integrity of
output cholinergic projection from PPN to both ascending
reticular activating system ARAS and auditory pathway. We believe
this is the first report of restoring the integrity of P1 wave
following posterior ansa-pallidotomy in patients with advanced
idiopathic Parkinson's disease. Disinhibition of the PPN by
posterior ansa-pallidotomy can explain improvements in motor
symptoms in view of reemergence and normalization of P1 wave
form.
1996/12
1996/01 00:00
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TITLE: Simultaneous bilateral pallidoansotomy for
idiopathic dystonia musculorum deformans.
AUTHORS: Iacono RP; Kuniyoshi SM; Lonser RR; Maeda G; Inae AM;
Ashwal S
AUTHOR AFFILIATION: Department of Surgery, University School of
Medicine, CA 92350, USA.
SOURCE: Pediatr Neurol 1996 Feb;14(2):145-8
CITATION IDS: PMID: 8703227 UI: 96269072
ABSTRACT: A 17-year-old Russian male with a 9-year diagnosed
history of dystonia musculorum deformans manifested as severe
tortipelvis, lordosis, and axial and appendicular spastic
dystonia, refractory to medical therapy, is reported. This
patient underwent a simultaneous bilateral pallidoansotomy with
dramatic results. Postoperative evaluation revealed sustained
alleviation of all dystonic symptoms and abnormal movements.
Rapid recovery of useful strength in all limbs as well as
dramatic improvement in coordination occurred. Bilateral
posteroventral pallidotomy and pallidoansotomy in the past have
proven effective in alleviation of all parkinsonian symptoms,
including dyskinesia and dystonia, without the concurrent risk of
intransigent side effects associated with bilateral thalamotomy
or other stereotactic surgical procedures. Pallidoansotomy may
prove to be the treatment of choice for idiopathic torsion
dystonia and merits further investigation.
1996/02
1996/01 00:00
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TITLE: The results, indications, and physiology of
posteroventral pallidotomy for patients with Parkinson's disease
[see comments]
AUTHORS: Iacono RP; Shima F; Lonser RR; Kuniyoshi S; Maeda G;
Yamada S
AUTHOR AFFILIATION: Clinical Neuroscience Research Group, Loma
Linda University Medical Center, California, USA.
SOURCE: Neurosurgery 1995 Jun;36(6):1118-25; discussion 1125-7
CITATION IDS: PMID: 7643990 UI: 95371827
COMMENT: Comment in: Neurosurgery 1995 Jun;36(6):1154-7
ABSTRACT: In the past, stereotactic surgical intervention for
Parkinson's disease was considered indicated only in those
patients with active motor manifestations that were refractory to
pharmacological therapy, manifestations such as tremor, rigidity,
dystonia, and dyskinesia. With the reintroduction and refinement
of Leksell's posteroventral pallidotomy, both akinetic and
hyperkinetic symptoms are now amenable to surgical treatment. We
have analyzed the results of 126 patients who underwent either
unilateral (n = 58) or bilateral (n = 68) posteroventral
pallidotomies. The Unified Parkinson's Disease Rating Scale and
Hoehn and Yahr Staging Scale were used for preoperative and
postoperative objective assessments. Postoperative follow-up
evaluation occurred initially at 1 week and subsequently at
intervals between 1 and 12 months (mean = 4.5 months) after
surgery. Although individual motor subscores on the Unified
Parkinson's Disease Rating Scale were significantly reduced (n =
126, P < or = 0.01), the most dramatic findings were the
reversal of akinetic symptoms and the elimination of dyskinesia
and profound "off" periods. These clinical results,
combined with intraoperative microelectrode records revealing
pallidal neuronal hyperactivity, suggest a reconsideration of the
pathophysiology of akinesia and point to possible mechanisms of
akinesia improvement by posteroventral pallidotomy in some
parkinsonian subgroups.
1995/06
1995/01 00:00
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TITLE: New pathophysiology of Parkinson's disease
revealed by posteroventral pallidotomy.
AUTHORS: Iacono RP; Lonser RR; Oh A; Yamada S
AUTHOR AFFILIATION: Department of Surgery, Loma Linda University
Medical Center, CA 92350, USA.
SOURCE: Neurol Res 1995 Jun;17(3):178-80
CITATION IDS: PMID: 7643972 UI: 95371808
ABSTRACT: Since the failure of levodopa therapy to maintain
long-term symptom relief in Parkinson's disease, posteroventral
pallidotomy has seen a dramatic increase in use and interest. It
has significantly reduced both the akinetic and hyperkinetic
symptoms of Parkinson's disease while requiring most patients to
maintain preoperative levodopa doses. Here we review the clinical
results of over 300 posteroventral pallidotomies and
pathophysiology of Parkinson's disease in relationship to
different neurotransmitters and medical therapy.
1995/06
1995/01 00:00
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TITLE: Combined stereotactic thalamotomy and
posteroventral pallidotomy for Parkinson's disease.
AUTHORS: Iacono RP; Henderson JM; Lonser RR
AUTHOR AFFILIATION: Division of Neurosurgery, Loma Linda
University Medical Center, California, USA.
SOURCE: J Image Guid Surg 1995;1(3):133-40
CITATION IDS: PMID: 9079438 UI: 97233249
ABSTRACT: Stereotactic thalamotomy has traditionally provided
good relief of tremor for patients with intractable
tremor-dominant Parkinson's disease. However, bradykinesia,
dyskinesia, and rigidity are often less reliably treated with
this technique. Although posteroventral pallidotomy (PVP) can
alleviate dyskinesias, appendicular bradykinesia, and rigidity,
tremor may not be completely ameliorated. We have combined
Vim/VOp junction thalamotomy and PVP in 29 patients with severe
tremor, rigidity, and bradykinesia. Patients underwent unilateral
Vim thalamotomy followed at the same sitting by PVP. The distinct
physiological consequences of each procedure were documented by
intraoperative electromyography (EMG) and video recording,
revealing the effects on both tremor and agonist/antagonist
co-contraction. Lack of reciprocal inhibition of antagonistic
muscle groups often remained following thalamotomy but was
eliminated by subsequent PVP. The complementary therapeutic
effects of PVP and Vim thalamotomy may be due to the interruption
of different neuronal circuits by the two procedures. The effect
of Vim thalamotomy has been attributed to the interruption of the
rubrothalamocortical loop. PVP interrupts the outflow of the
globus pallidus interna (GPi), which may cause disinhibition of
locomotor centers in the mesencephalon and spinal cord. There is
no direct interruption of the rubrothalamocortical loop by PVP,
explaining why this procedure sometimes exacerbates tremor in
certain patients. The combination of the two procedures appears
to provide excellent relief of the majority of symptoms in
patients suffering from tremor-dominant Parkinson's disease.
1995/01
1995/01 00:00
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TITLE: Comparison of MRI and ventriculographic target
acquisition for posteroventral pallidotomy.
AUTHORS: Mandybur G; Morenski J; Kuniyoshi S; Iacono RP
AUTHOR AFFILIATION: Division of Neurosurgery, Loma Linda
University Medical Center, Calif., USA.
SOURCE: Stereotact Funct Neurosurg 1995;65(1-4):54-9
CITATION IDS: PMID: 8916330 UI: 97073621
ABSTRACT: The true accuracy of MRI scanners utilized for target
acquisition in functional stereotaxis remains undefined. We have
performed pallidotomies at the Loma Linda University Medical
Center using both MRI and MRI concomitant with positive contrast
ventriculography. A retrospective study of 33 cases revealed
significant differences in coordinates obtained by MRI alone and
MRI concomitant with ventriculography (antero-posterior
coordinates, mean error: 2.6 mm, range 0.5-6.8 mm; Z coordinates:
mean error 4.6 mm, range 0-19 mm). While MRI promises excellent
target identification, the generated target coordinates
significantly stray from the optimal target. Ventriculography
corrects the MRI coordinates and demonstrates the position of the
radiofrequency probe with respect to the target and anatomic
reference points.
1995/01
1995/01 00:00
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TITLE: Unilateral versus bilateral simultaneous
posteroventral pallidotomy in subgroups of patients with
Parkinson's disease.
AUTHORS: Iacono RP; Lonser RR; Kuniyoshi S
AUTHOR AFFILIATION: Division of Neurosurgery, Loma Linda
University Medical Center, Calif., USA.
SOURCE: Stereotact Funct Neurosurg 1995;65(1-4):6-9
CITATION IDS: PMID: 8916322 UI: 97073613
ABSTRACT: Despite the bilateral appendicular symptoms of
Parkinson's disease, bilateral surgical interventions in the
basal ganglia have been shunned because of cognitive and speech
disturbances following bilateral thalamotomy. However, we present
the uncomplicated results of 25 simultaneous posteroventral
pallidotomies and compare their obvious superior control of
appendicular symptoms as well as axial symptoms with the results
of 25 unilateral posteroventral pallidotomies.
1995/01
1995/01 00:00
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