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Unilateral Combined Stereotactic Radiofrequency
Pallidotomy And Thalamotomy For Idiopathic
Parkinson’s Disease’. A Prospective Observational
Study With 24-Month Follow-Up
Mohamed Khaled Elkazaz ( Mohamed.elkazaz@med.suez.edu.eg )
Suez Canal University https://orcid.org/0000-0002-7290-5744
Ali Salah Khedr
Suez Canal University
Maha Abd El Fattah
Suez Canal University
Research
Keywords: Parkinson’s disease, Thalamotomy, Pallidotomy, Tremors, Spasticity, Stereotaxis,
Radiofrequency
DOI: https://doi.org/10.21203/rs.3.rs-525235/v1
License: This work is licensed under a Creative Commons Attribution 4.0 International License.
Read Full License
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Abstract
Study Design: Prospective study
Objective: To report ecacy of unilateral combined stereotactic radiofrequency pallidotomy and
thalamotomy for Idiopathic Parkinson’s disease.
Methods: Between June 2017 to December 2019, 62 patients with idiopathic Parkinson’s disease
underwent stereotactic radiofrequency pallidotomy and thalamotomy. Pre-operatively clinical assessment
using the UPDRS and Hoen and Yahr scale for PD. Post-operatively clinical assessment using the UPDRS
and Hoen and Yahr scale for PD, complications in 1,6,12 and 24 months.
Results: 60 patients completed two-year follow-up and fullled our criteria were recruited. The mean age
was 57.47±9.90. The average UPDRS off motor assessment results showed reduction after 1 month from
60.16 to 30.88 and at 24-month follow-up was 41.6. The average Yahr and Hoen scale 3.63 to 1.19 after
1-month and 24 months was 1.87. The average UPDRS constancy of tremors improved after 1-month
from 3.53 to 0.75. Improvement in constancy of tremors reached 75% of cases after 24-month with
average 1.62. the average UPDRS rigidity score improved at 1-month follow-up from 3.31 to 1.21. Total
improvement of rigidity reached 63% after 24-month. 2 patients had post-operative thalamic hematoma
presented with hemiplegia, which was conservatively managed, and improved after 1-month with little
decit. 51.6% had gait imbalance at 6-month follow-up. 22.5% showed dysarthria immediately while
12.9% totally resolved after 1-month follow-up. No recorded cases of infection, CSF leaks or cognitive
dysfunction.
Conclusion: Our data suggest that Unilateral combined stereotactic radiofrequency pallidotomy and
thalamotomy for Idiopathic PD is effective procedure.
Introduction
Lesioning surgeries in PD include target obliteration of a certain area in brain tissue in to disrupt
maladaptive neuronal arrangements. An advancement in movement disorders when stereotactic
procedures in lesioning were applied. Target selections were modulated various times until in 1960s when
thalamotomy was used for tremors and pallidotomy was used for Bradykinesia and rigidity. (1, 2)
Though lesioning procedure was executed for numerous years in particular patients with PD, their
practice reduced in the 1960s following the presentation of levodopa. However, long term treatment with
L-dopa has led to newly unfavorable side effects that refreshed the era of lesion surgeries.(3)
Lesioning procedures has since developed, and presently accessible methods include invasive
procedures such as thermoablation, radiofrequency (RF) and laser interstitial thermal therapy (LITT). And
less invasive ones such as MRI-guided high-intensity focused ultrasound (HIFU) thermal ablation (or MR-
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guided focused ultrasound, MRgFUS), stereotactic radiosurgery (SRS with the radiofrequency and
thermaoablation are commonly used.(4, 5)
In 1954, Hassler and Reichert (2)used thalamotomy to treat tremor associated with Parkinson's disease
(PD). Ventrolateral thalamotomy has been considered to be the neurosurgical treatment of choice for
disabling, drug-resistant parkinsonian and other types of tremor that tremor can be relieved not only by a
thalamic lesion but also by a lesion in the posteroventral portion of the medial (internal) globus pallidum
and ventralis intermedius (VIM) nucleus of the thalamus. Hassler and Reichert, In 1945, Proved that
thalamotomy controls the tremors related to PD. Various studies had shown the role of VIM lesioning in
control of PD medically refractory tremors or other types of tremors. (6–8).
One of the studies reviewed retrospectively the results in 60 patients with PD tremors, cerebellar tremors,
essential tremor and post-traumatic tremor. These patients all had unilateral Vim thalamotomy. The
mean follow-up of 53.4 months, PD tremors had marked improvement in 86% of the cases. essential
tremor patients had similar improvement in 83% of cases. Results were not as favorable as PD tremors
and essential tremors for those patients with post-traumatic tremor (50%) or cerebellar tremor (67%).
Temporarily complications of thalamotomy were seen in 60% of cases includes dysarthria, dysphasia,
confusion, dystonia, contralateral paresis or sensory disturbances. (9)
Lesion of the posteroventral segment of the internal globus pallidus (GPi) is ecient at treating
contralateral tremor, rigidity, dyskinesia and bradykinesia. (10) Studies various studies proved this
opinion. The rst of these studies described an improvement in the off-state UPDRS motor score of 71%
at 1 year following the surgery. (11) Lozano et al. (12)UPDRS motor score improved in the off-state by
30% 6 months post operatively, although the UPDRS akinesia score improved only by 33%. The gait score
showed 15% improvement in the off-state and decrease in contralateral dyskinesias by 92%. Baron et al.
(13), described a 25% improvement in the motor score in the off-state by 25% 3 months post operatively.
Shannon et al. (14) described an improvement in 15% in the off-state motor score 6 months post
operatively.
Patients And Methods
This prospective observational study for patients suffering from Idiopathic Parkinson’s disease at Suez
Canal University institution through June 2017 to January 2019. Total number of 62 patients underwent
stereotactic unilateral combined pallidotomy “GPi” and Thalamotomy “Vim” using radiofrequency
ablation for the management of Parkinson related tremors, bradykinesia and rigidity after careful
counselling and acquiring consent from the patients. All patients have signed a consent for the
publication purpose. This article followed the world medical association declaration of Helsinki ethical
principles. Inclusion criteria included patients only diagnosed with idiopathic PD, with medication induced
motor signs and refractory tremor and Hoehn and Yahr > 2 stage off stage. Exclusion criteria included
multiple comorbidities that increases morbidity and mortality risk of the surgery, Neuropsychiatric
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diseases, Dementia, postural instability and atypical PD “supranuclear gaze palsy, early postural
instability or severe early dysautonomia”. Failure to proceed to 24-month follow-up.
A multidisciplinary presurgical assessment is done by neurosurgeon and neurology team was a complete
physical and mental assessment to the patients presented with PD. Neurology team was responsible for
diagnosis conrmation and assessment of the medication trials the patients were offered. The off state
was outlined as the state after withdrawal by 12 hours of anti PD treatment based in the Core
assessment program for intracerebral transplantation committee denition (CAPIT). (15) UPDRS off state
motor assessment was used in the following items in off state; medication induced dyskinesia pre- and
post-operatively immediate, 6 months and 2 year.(16) Patients were also staged in Hoehn and Yahr scale
in off state pre- and post-operatively immediate, 6 months and 1 year.(17) Preoperative brain imaging
included an MRI and a CT brain one day prior to surgery.
Operative details
After admission patients are pre-operatively assessed by anesthesia team. Stereotactic system
application “CRW” system is used under local anesthesia by scalp block. Patients then underwent CT
brain with the frame and ducials applied to it. Data is analyzed and target selection is done by waypoint
navigator software FHC corporation selecting the preference points after fusion between preoperative
MRI, CT brain and post ducials CT brain as follows.
Target selection
Vim target from the posterior commissural point with 14 mm lateral, 6 mm anterior in the same AC-PC
plane (Fig. 1) and GPi point from the mid commissural point is 21 mm lateral and 3 mm anterior to it at
the MC plane (Fig. 1). Specic adjustments are done in relation to the lateral ventricular wall and internal
capsule with the fusion images. Following, targets are transferred to Stereocheck ios by Moris (Fig. 2)
application and target data acquisition is done in Entry, target X,Y,Z. preoperative placement of the patient
on the Mayeld. Patients is connected with neurophysiology monitoring for motor assessment. Sterile
shaving and surgical draping is done. Data gained from Stereocheck is then transferred to phantom
stereotaxis system and conrmed then the arc and ring is xed upon patients’ frame. Burr hole guided by
trajectory from the software then durotomy.
Electrode placement
Insertion of the macroelectrode with bipolar 2-mm width, 3-mm length and 3-mm tip through a guiding
tube with 2mm diameter of the radiofrequency apparatus “Neuro N50 by Inomed” with impedance
monitoring.
Functional localization is done by Macrostimulation with 2 Hz and 50 Hz in both points to assess
proximity of the Vim target to VC and internal capsule and GPi target to its proximity to internal capsule.
After conrmation of the target Vim underwent a temporarily lesioning “50C for 50 seconds’ followed by
careful assessment of the patient if no decit then followed by permanent lesion “65 C for 60 seconds”
withdraw by 2-mm and reapply permanent lesion. Gpi underwent a temporarily lesioning “50 C for 50
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seconds’ followed by careful assessment of the patient then followed by permanent lesion “72 C for 60
seconds” withdrawal by 2-mm then reapply permanent lesion. Hemostasis and skin closure are done.
Post-operative assessment is done in 6-month and 2-year assessments for the UPDRS off state motor
assessment and Hoehn and Yahr scale. Intra and Post-operative complications are reported.
Statistical analysis was done by SPSS IOS v26. paired t-test was implemented between means of
variables.
Results
62 patients were enrolled in the study, 37 male and 25 females and the mean age is 57.47 ± 9.90. 2
patients failed to follow-up and excluded from the study.
The average UPDRS off motor assessment results showed marked reduction after 1 month from 60.16 to
30.88 (Table 1). At 6-month and 1-year follow-ups there was a non-signicant rise in the average UPDRS
off motor assessment to 39.1 and 42.3 respectively. At 24-month follow-up the average UPDRS off motor
was 41.6. The average Yahr and Hoen scale 3.63 to 1.19 after 1-month follow-up (Table 1). At 6-month
and 12-month follow-ups there was a non-signicant rise to 1.5 and 1.9. 24 months post-operatively the
average Yahr and Hoen scale was 1.87. (Graph 1 and 2)
Table 1
Clinical assessment pre-operative and the nal follow-up (24-month) later
Item Pre-operative 24-month t-score
p
-value
UPDRS off state motor score 60.16 ± 3.8 41.6 ± 4.49 10.23 < 0.05*
Yahr and Hoehn scale 3.63 ± 0.66 1.87 ± 0.61 7.8 < 0.05*
Results are in mean ± SD.
*p-value < 0.05 is statistically signicant at condence interval 95%.
The average UPDRS constancy of tremors (Graph 3) were analyzed and showed a signicant
improvement after 1-month duration 3.53 to 0.75. There was a non-signicant rise in 6,12 to 1.23 and
1.72 respectively. Total improvement in constancy of tremors reached up to 75% of cases after 24-month
with average 1.62
In addition, the average UPDRS rigidity score (Graph 4) also showed signicant improvement at 1-month
follow-up from 3.31 to 1.21. There was a non-signicant rise in 6,12 to 1.9 and 2.3. At 24-month follow-up
the average reached 2.1. Total improvement of rigidity reached up to 63% of cases after 24-month.
2 patients (3.2%) had thalamic hematoma that was discovered post-operatively with hemiplegia (Fig. 3)
which was conservatively managed, and patients improved after 1-month with little residual decit. Also
noticed in the study that 32 patients (51.6%) had gait imbalance noticed at 6-month follow-up with
leaning towards the contralateral side to the lesioning. 14 patients (22.5%) of cases showed dysarthria
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immediately post-operative where 8 patients (12.9%) totally resolved after 1-month follow-up. No
recorded cases of infection, CSF leaks or cognitive dysfunction.
Discussion
Spiegel et al. in 1947 introduced the era of brain stereotactic surgery.(18) Later it became an evolution in
this eld in the management of PD. Hassler successfully managed to control PD symptoms by
thalamotomy.(19) Traditionally, thalamotomy alone was used as a maneuver for PD. But after Leksell’s
evolutionary introduction to the Gpi lesioning rigidity and bradykinesia were managed along with tremors.
(6) Long term studies on isolated thalamotomies had shown that patients are still disabled with rigidity.
In addition studies which favored isolated lesion in GPi can control both rigidity and tremors that was
found later to be insucnet to control the tremors.(20, 21) Vim lesioning aims to disrupt the
rubrothalamocortical circuit controlling abnormal impulses initiating tremors.(22, 23) while GPi lesioning
disconnect the inhibitory outow of the Gpi to the VOa nucleus and the PPN. (22, 24)
In this series we had a success rate in improving patients UPDRS and experiencing less relapse and
complications. Marcelo et al. reported improvement of thalamotomy procedure in suppressing tremors in
PD with 75% in upper limb and 73% in lower limb tremors.(25)
Fayed et al. reported successful results in combined pallidotomy and thalamotomy over pallidotomy
alone in improving patients functional state and controlling PD.(26) Several mechanisms were postulated
regarding the persistence of tremors after lesioning the Gpi alone as the Gpi lesion does not directly
disconnect the rubrothalamocortical loop as it may exacerbate by the disinhibition of the reticulospineal
system. (23, 27) Locano et al. stated that combined Vim and GPi lesioning can treat broad range of
symptoms in PD immediately with no or little risk on the patients.(22)
Conclusion
Unilateral combined Vim/Gpi had shown to be very effective in controlling PD symptoms and improve the
overall functional state of the patients. Despite a successful technique, few studies were involved in it. It
showed to be potent and carries little risk for the patients. We advocate that case-control studies should
be directed to assess this technique.
Limitations
The small sample size affected the statistical testing of the results.
Abbreviations
CAPIT: Core assessment program for intracerebral transplantation committee
CRW: Cosman Roberts Wells
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CSF: cerebrospinal uid
CT: Computed tomography
GPi: Globus pallidus internus
HIFU: High-intensity focused ultrasound
LITT: laser interstitial thermal therapy
MRgFUS: Magnetic resonance -guided focused ultrasound
MRI: Magnetic resonance imaging
PD: Parkinson’s Disease
RF: Radiofrequency
UPDRS: Unied Parkinson’s disease rating scale
Vim: Ventralis intermedius
Declarations
Ethics approval and consent to participate
This research was revised and accepted by the research committee in Suez Canal University hospitals
and accepted. Patients were consented in written format before entering the study for undergoing the
procedure and publication purposes.
Consent for Publications
Patients were consented for the publication purpose of their medical data.
Availability of data and materials
The datasets used in this research are available in the neurosurgical department, Suez Canal University
and are available upon requested
Competing interests
The authors declare that they have no competing interests.
Funding
There is no funding for this research
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Authors contribution
M.E, Investigation and Formal analysis of the data and writing original draft.
A.KSurgical planning and execution, Methodology, Resources, Validation, writing review and editing,
supervision and Project administration
M.A Writing review and editing and planning Physiotherapeutic plan for the patients.
Acknowledgments
Special thanks to the Neurosurgery department in Suez Canal University for the continuous support.
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Figures
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Figure 1
Case presentation 56 male patient with PD planning for right unilateral combined Vim and Gpi lesioning.
A, axial MRI brain T1W with Vim target “red crosshair right to third ventricle”. B, Coronal MRI brain T1W
with Vim target “red crosshair right to third ventricle”. C, axial MRI brain T1W with Gpi target “red
crosshair right to third ventricle”. D, Coronal MRI brain T1W with Gpi target “red crosshair right to third
ventricle”.
Figure 2
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Axial CT brain with ring and ducial marks for planning in Stereocheck ios by Moris.
Figure 3
A, Coronal CT brain with thalamic hematoma post-lesioning. B, Axial CT
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Figure 4
Graph1: UPDRS off motor state assessment.
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Figure 5
Graph2: Yahr and Hoen assessment
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Figure 6
Graph3: UPDRS constancy of rest tremors assessment
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Figure 7
Graph4: UPDRS rigidity assessment
