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Case Report on Deep Brain Stimulation Rescue After Suboptimal MR-Guided Focused Ultrasound Thalamotomy for Essential Tremor: A Tractography-Based Investigation


Abstract and Figures

Essential tremor (ET) is the most prevalent movement disorder in adults, and can often be medically refractory, requiring surgical intervention. MRI-guided focused ultrasound (MRgFUS) is a less invasive procedure that uses ultrasonic waves to induce lesions in the ventralis intermedius nucleus (VIM) to treat refractory ET. As with all procedures for treating ET, optimal targeting during MRgFUS is essential for efficacy and durability. Various studies have reported cases of tremor recurrence following MRgFUS and long-term outcome data is limited to 3–4 years. We present a tractography-based investigation on a case of DBS rescue for medically refractory ET that was treated with MRgFUS that was interrupted due to the development of dysarthria during the procedure. After initial improvement, her hand tremor started to recur within 6 months after treatment, and bilateral DBS was performed targeting the VIM 24 months after MRgFUS. DBS induced long-term tremor control with monopolar stimulation. Diffusion MRI tractography was used to reconstruct the dentatorubrothalamic (DRTT) and corticothalmic (CTT) tracts being modulated by the procedures to understand the variability in efficacy between MRgFUS and DBS in treating ET in our patient. By comparing the MRgFUS lesion and DBS volume of activated tissue (VAT), we found that the MRgFUS lesion was located ventromedially to the VAT, and was less than 10% of the size of the VAT. While the lesion encompassed the same proportion of DRTT streamlines, it encompassed fewer CTT streamlines than the VAT. Our findings indicate the need for further investigation of targeting the CTT when using neuromodulatory procedures to treat refractory ET for more permanent tremor relief.
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fnhum-14-00191 June 26, 2020 Time: 17:38 # 1
published: 26 June 2020
doi: 10.3389/fnhum.2020.00191
Edited by:
Chella Kamarajan,
SUNY Downstate Medical Center,
United States
Reviewed by:
Sagi Harnof,
Rabin Medical Center, Israel
Idit Tamir,
Rabin Medical Center, Israel, in
collaboration with reviewer SH
Manish Ranjan,
West Virginia University, United States
Casey H. Halpern
Specialty section:
This article was submitted to
Brain Imaging and Stimulation,
a section of the journal
Frontiers in Human Neuroscience
Received: 20 February 2020
Accepted: 28 April 2020
Published: 26 June 2020
Saluja S, Barbosa DAN, Parker JJ,
Huang Y, Jensen MR, Ngo V,
Santini VE, Pauly KB, Ghanouni P,
McNab JA and Halpern CH (2020)
Case Report on Deep Brain
Stimulation Rescue After Suboptimal
MR-Guided Focused Ultrasound
Thalamotomy for Essential Tremor: A
Tractography-Based Investigation.
Front. Hum. Neurosci. 14:191.
doi: 10.3389/fnhum.2020.00191
Case Report on Deep Brain
Stimulation Rescue After Suboptimal
MR-Guided Focused Ultrasound
Thalamotomy for Essential Tremor: A
Tractography-Based Investigation
Sabir Saluja1, Daniel A. N. Barbosa1, Jonathon J. Parker1, Yuhao Huang1,
Michael R. Jensen1, Vyvian Ngo1, Veronica E. Santini2, Kim Butts Pauly3,
Pejman Ghanouni3, Jennifer A. McNab3and Casey H. Halpern1*
1Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, United States, 2Department
of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, United States, 3Department
of Radiology, Stanford University School of Medicine, Stanford, CA, United States
Essential tremor (ET) is the most prevalent movement disorder in adults, and can often
be medically refractory, requiring surgical intervention. MRI-guided focused ultrasound
(MRgFUS) is a less invasive procedure that uses ultrasonic waves to induce lesions in
the ventralis intermedius nucleus (VIM) to treat refractory ET. As with all procedures for
treating ET, optimal targeting during MRgFUS is essential for efficacy and durability.
Various studies have reported cases of tremor recurrence following MRgFUS and
long-term outcome data is limited to 3–4 years. We present a tractography-based
investigation on a case of DBS rescue for medically refractory ET that was treated
with MRgFUS that was interrupted due to the development of dysarthria during
the procedure. After initial improvement, her hand tremor started to recur within 6
months after treatment, and bilateral DBS was performed targeting the VIM 24 months
after MRgFUS. DBS induced long-term tremor control with monopolar stimulation.
Diffusion MRI tractography was used to reconstruct the dentatorubrothalamic (DRTT)
and corticothalmic (CTT) tracts being modulated by the procedures to understand
the variability in efficacy between MRgFUS and DBS in treating ET in our patient. By
comparing the MRgFUS lesion and DBS volume of activated tissue (VAT), we found that
the MRgFUS lesion was located ventromedially to the VAT, and was less than 10% of the
size of the VAT. While the lesion encompassed the same proportion of DRTT streamlines,
it encompassed fewer CTT streamlines than the VAT. Our findings indicate the need for
further investigation of targeting the CTT when using neuromodulatory procedures to
treat refractory ET for more permanent tremor relief.
Keywords: essential tremor, focused ultrasound, deep brain stimulation, tractography, thalamus, MRI
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Saluja et al. DBS Rescues MRgFUS for ET
Essential tremor (ET) is the most prevalent movement disorder in
adults. Treatment options for medically refractory cases include a
variety of ablative and deep brain stimulation (DBS) procedures,
usually targeting the ventralis intermedius (VIM) nucleus of the
thalamus (Flora et al., 2010;Louis and Ferreira, 2010).
Recently, Elias et al. (2016) reported the results of a
randomized control trial demonstrating the efficacy of unilateral
MRI-guided focused ultrasound (MRgFUS) targeting the VIM
in treating refractory ET. Out of the 56 patients who received
MRgFUS thalamotomy of the VIM, 5 patients (8.9%) experienced
the return of their tremor symptoms within 12 months
postoperatively, with tremor scores worsening by 23% (Elias
et al., 2016). In a 2-year follow up study, however, 4% of the
original cohort subsequently received DBS due to unsuccessful
or suboptimal treatment with MRgFUS (Chang et al., 2018).
A retrospective comparative evaluation of RF thalamotomy,
DBS, or MRgFUS for ET patients revealed this loss of effect
is shared across modalities (Halpern et al., 2019). Moreover,
compared to 6-months post-procedure, the 3-year follow-up
study found that even though the primary outcome metric
for the trial (i.e., the hand combined tremor-motor score) was
significantly improved, there was a slight but significant increase
in the median total Clinical Rating Scale for Tremor (CRST)
score over time (Kim et al., 2017). The mechanism for this
recrudescence remains elusive and is undoubtedly multifactorial,
but a detailed review of the anatomic aspects of a suboptimal
MRgFUS thalamotomy may guide the future management of
these patients (Ravikumar et al., 2017).
One approach for understanding this loss of efficacy is
utilizing diffusion-weighted MRI (dMRI) imaging to assess
the white-matter fiber tracts being modulated by MRgFUS.
Tractography studies have demonstrated that lesions must target
the cerebello-thalamo-cortical network for treatment of ET
(Coenen et al., 2014). The two major groups of white-matter
fiber tracts involved in this network are the dentatorubrothalamic
tract (DRTT) and the corticothalamic tract (CTT). These two
pathways have been found to be necessary targets for the
treatment of ET (Tian et al., 2018).
We present a tractography-based investigation of a patient
treated with MRgFUS thalamotomy for ET, whose procedure was
prematurely aborted due to new onset dysarthria. Immediately
post-procedure, the patient experienced tremor relief and the
dysarthria partially improved, but her tremor symptoms, most
notably hand tremor, began to return 6 months postoperatively.
The patient subsequently received DBS, and the surgery was
well-tolerated and efficacious at the long-term.
Using a multimodal imaging strategy, we reconstructed the
MRgFUS lesion and the volume of activated tissue (VAT)
produced by the DBS electrode and the patient’s specific
programming. We then used probabilistic tractography to assess
the relationships between the MRgFUS lesion, DBS VAT, and
the white matter fiber tracts associated with tremor control. This
methodology offers a unique understanding of the specific fiber
tracts modulated in both MRgFUS and DBS, in order to shed light
on why DBS yielded a better long-term outcome in our patient.
A 70-year-old female with medically refractory ET was evaluated
at our movement disorders clinic after nearly 30 years of tremor.
Her tremor began in her left hand and eventually progressed
to her right hand, head and voice. Eventually, she required
assistance for her activities of daily living, including eating,
writing, and dressing due to the severity of her tremor. She
tried numerous medication therapies including combinations
of propranolol, primodone, and gabapentin, in addition to
chemodenervation with botulinum toxin. Despite all treatment
attempts, she only achieved suboptimal tremor control.
At presentation, she was found to have postural tremors
bilaterally in her upper extremities, significantly worsening with
action and improving with rest. Her handwriting as well as her
straight line and spiral drawing tests were markedly abnormal
(Figure 1). She had head tremor and her voice was tremulous
with audible oscillations. Her bedside cognitive status, as assessed
by the Montreal Cognitive Assessment (MoCA) test, was within
normal limits. There was no evidence of parkinsonism on
examination. The CRST A subscore was 30 at the time of
presentation in 2015, reflecting her postural and kinetic tremors
(Figure 1). The patient presented with options of continued
medical management, bilateral DBS, unilateral DBS, or MRgFUS
as part of an ongoing clinical trial. At the time of initial
presentation and evaluation, the patient was most distressed by
her dominant hand tremor, and thus, after presented with the
options, elected to proceed with MRgFUS focused on relief for
her dominant upper extremity tremor.
The patient underwent a left MRgFUS thalamotomy in August
2015. The series of sonications is described in Supplementary
Table S1. The left VIM nucleus target was guided by 3T MRI
using standard coordinates from the mid-commissural point
(MCP): –13.3 mm, –6 mm, 0 mm (10 mm from the ventricular
wall) for sonications 1–19, 1 mm medial from the canonical
stereotactic target. This target was chosen to provide about 2 mm
of a safety margin from the thalamo-capsular boundary based on
the patient’s preoperative MRI imaging. There were adjustments
to the location of the sonication’s focus in order to sonicate
the center of the planned target. By sonication 19, the patient’s
tremor was largely relieved, but the lesion’s boundaries were
approaching the internal capsule. For sonication 20, the target
was moved 1 mm medially to avoid the internal capsule. For
final sonication 21, the target was moved an additional 1 mm
medial to continue the ablation but ensure no breach of the
internal capsule. At the conclusion of sonication 21, transient
dysarthria was noted on the patient’s clinical examination,
and the procedure was terminated. Out of the 21 sonications
performed, four of them reached a temperature greater than
55C, and the maximum temperature attained was 61C. The
highest energy sonication reached 15940 J (797 W for 20 s). The
SDR was 0.51. There were no cavitations. The procedure was
aborted due to new-onset dysarthria. The patient experienced
a significant improvement in her tremor at 2-week follow-up.
Her only new symptom was transient dysarthria that initiated
during MRgFUS treatment. Over the next 6 months, however,
she noticed progressive tremor recurrence and worsening of
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Saluja et al. DBS Rescues MRgFUS for ET
FIGURE 1 | (A) Clinical timeline of patient’s procedures and DBS programming parameters following FUS and lead implantation. The patient’s tremor was evaluated
using the Clinical Rating Scale for Tremor (CRST) A subsection, which evaluates tremor, including those of the upper extremities. (B) “Archimedes spiral” drawings
(right hand only) during the B subsection of the CRST assessment to evaluate hand tremor at each time point to demonstrate tremor progression over time after
MRgFUS procedure. Spiral A is wide, compared to the narrow spiral B (acquired as part of the CRST B).
her tremor symptoms despite partial improvement of dysarthria
(see Supplementary Table S2).
After discussion with and further evaluation of the patient
through a multidisciplinary DBS review board, she was deemed
a candidate for DBS targeted to the VIM nucleus. Approximately
24 months after her initial left MRgFUS, DBS (Medtronic
Activa PC) leads were bilaterally placed without complication
using frameless robotic-assisted stereotactic navigation (Ho et al.,
2019). Based on the dysarthria previously experienced that
was presumed to be due to the relatively medial location of
the MRgFUS treatment, DBS leads were placed using target
coordinates of -13, -6.5, and 0 mm from the MCP (5.9 mm
anterior to PC). The target was more lateral in order to
minimize dysarthria, and more posterior so that the trajectory
did not enter blood vessels, ventricles, or sulci. Intraoperative
electrophysiological monitoring and postoperative imaging
demonstrated satisfactory lead placement. A standard monopolar
testing protocol was performed to evaluate the threshold of
efficacy for each contact and any adverse effects. With stimulation
at 1.5 V, there were no adverse effects with activation of
contacts C1-C3, however, the patient experienced transient right
lip paresthesia with activation of left hemisphere contact C0,
which was the contact located closest to the MRgFUS lesion.
At 3–4 V, the patient experienced slight dysarthria when left
hemisphere contact C1 was activated. When C1 in the right
hemisphere was activated at 3.0 V, her dysarthria worsened.
Contact C2 was chosen for monopolar activation at 2.7 V
in the left hemisphere and 2.0 V in the right hemisphere,
which maximized her tremor suppression and minimized adverse
effects. At her last evaluation (16-month follow-up after DBS),
she had consistent and effective tremor control, with a CRST
score of 7 (Figure 1). The left lead was active at contact 2
set at 2.8 V, pulse width 60 ms and 100 Hz. The right lead
was active at electrode 10 set at 2.3 V, pulse width 60 ms
and 100 Hz. The patient had excellent tremor suppression
following monopolar activation of the DBS leads, as shown
by sustained decrease in CRST and significant improvement
drawing coherent spirals.
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Saluja et al. DBS Rescues MRgFUS for ET
MRI Imaging Acquisition and
T1-weighted and T2-weighted structural 3T MRI images were
acquired before and after FUS. Diffusion-weighted images were
acquired from the patient before MRgFUS (3T, 2 mm isotropic,
TR/TE = 8500/81.6 ms, b = 2500 s/mm2, 60 directions,
582 s) and before DBS implantation (3T, 2 mm isotropic,
TR/TE = 8000/60.7 ms, b = 1000 s/mm2, 30 directions, 502 s).
Computed tomography (CT) images with 1 mm slice thickness
were obtained postoperatively after DBS implantation. FSLs
“topup” tool was used to estimate and correct non-zero off-
resonance fields caused by susceptibility distribution of the
subject’s head via analysis of forward and reverse phase encoded
B0image acquisitions (Andersson et al., 2003). FSLs “eddy” tool
was used to correct for the eddy current caused by rapid switching
on and off of the diffusion gradient (Smith et al., 2004).
Lesion Volume, Electrode
Reconstruction, and Volume of Activated
Tissue Estimation
MRgFUS results in three distinct zones of ablation that can be
viewed on a T2-weighted image (Wintermark et al., 2014). The
lesion region of interest (ROI) was created by including the voxels
that are within the two inner zones (the third outer zone being
vasogenic edema) on an MRI acquired the same day following
MRgFUS thalamotomy. Lead-DBS was used for localization and
visualization of the DBS electrode contacts (Horn et al., 2019).
Linear and nonlinear transformations were computed from the
MNI 152 2009c template to the T1 and T2-weighted images,
as well as the postoperative CT. The DBS Intrinsic Template
Atlas (DISTAL) was subsequently transformed onto the native
T1-weighted images and used to localize the electrodes as well
as the MRgFUS lesion in reference to the VIM (Ewert et al.,
2018). The VAT was estimated using a finite element modeling
method based on the characteristics of the brain tissue activated
and the DBS programming voltage and estimated impedance
(Madler and Coenen, 2012).
Probabilistic Tractography and
Statistical Analysis
Tractography was performed with MRtrix using constrained
spherical deconvolution to estimate the white-matter fiber
orientation distribution from the diffusion signal of the dMRI
images (Smith et al., 2013). Using probabilistic tractography,
the DRTT was filtered to include white-matter tracts that
are seeded at the dentate nucleus and terminate in the
thalamus, along with sending collaterals to the red nucleus.
Freesurfer was used to segment the structural T1-weighted
images to generate ROIs for the thalamus, and dentate
nucleus (Desikan et al., 2006;Fischl, 2012). The red nucleus
was drawn using guidance from an expert neuroradiologist.
The CTT was filtered to include only white-matter tracts
seeded at the precentral gyrus and terminate at the thalamus.
Freesurfer was used to generate masks encompassing the
precentral gyrus.
A mask of the MRgFUS lesion was overlaid on the pre-
MRgFUS tractography streamlines, and a mask of the VAT
was overlaid onto the pre-DBS streamlines. The proportion of
streamlines of each tract that were incorporated by the lesion and
VAT were calculated by dividing the raw number of streamlines
of the DRTT and CTT that intersected the lesion and VAT, by the
total number of streamlines within the DRTT and CTT.
The MRgFUS lesioning procedure in the VIM resulted in
immediate tremor suppression. The patient’s CRST A score
decreased from 30 to 18 as a result. Her tremor suppression
remained stable for 6 months, then began worsening. Twenty-
four months after the MRgFUS procedure, the patient’s CRST A
score had increased to 28, and at this time, the patient received
DBS electrode implantation. Subsequent programming reduced
her tremor, resulting in a CRST A score of 7 after optimizing DBS
programming parameters.
Probabilistic tractography reconstructed streamlines of the
DRTT (Figure 2) and CTT (Figure 3) for the pre-FUS (A)
and pre-DBS (B) diffusion weighted images. The lesion after
MRgFUS, and the VAT from DBS, were overlaid onto each
respective image to select the voxels that were modulated
by each modality.
The MRgFUS lesion’s volume was calculated to be 20.28 mm3.
The estimated VAT from the unilateral left VIM DBS at the
patient’s last programming settings was 233.16 mm3. The VAT’s
x, y, and z coordinates relative to the MCP were -15.5, -2.5, and
-7 mm. The center of the lesion was located 3.75 mm closer to the
midline than the active DBS VAT, and 5 mm more ventral. The
lesion location in the pre-FUS image captured 12.9% of the DRTT
streamlines and 4.4% of the CTT streamlines, while the DBS VAT
location of the pre-DBS image encompassed 13.6% of the DRTT
streamlines and 29.7% of the CTT streamlines, respectively.
For visualization purposes, the lesion and VAT were
reconstructed in 3D alongside the DBS electrodes and the
internal and external nuclei of the VIM, defined by the DISTAL
atlas (Figure 4).
Tremor relief that is not sustained after MRgFUS treatment is
troublesome to patients and presents a significant management
challenge. For these patients in whom treatment has failed, it
may be appropriate to offer repeat or rescue procedures (Tuleasca
et al., 2017;Wang et al., 2018;Weidman et al., 2019). However,
in the described case, the scant availability of repeat MRgFUS
efficacy, the side effect of dysarthria, and patient preference
for bilateral therapy made DBS a favorable alterative, not to
mention its ability to be used somewhat reversibly and bilaterally.
Using patient-specific probabilistic tractography, we investigated
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FIGURE 2 | The DRTT shown in the Pre-FUS and Post-FUS volumes. In (A), the lesion after MRgFUS was overlaid onto the pre-FUS image, to isolate the voxels that
encompassed the lesion before the MRgFUS procedure. In (B), the DBS VAT was overlaid onto the Pre-DBS image. The DRTT was isolated from all tracts generated
via probabilistic tractography by only including the streamlines that intersected the ROI masks for the cerebellum white matter (dentate nucleus), thalamus, and red
FIGURE 3 | The CTT shown in the Pre-FUS and Post-FUS volumes. In (A), the lesion after MRgFUS was overlaid onto the pre-FUS image, to isolate the voxels that
encompassed the lesion before the MRgFUS procedure. In (B), the DBS VAT was overlaid onto the Pre-DBS image. The CTT was isolated from all tracts generated
via probabilistic tractography by only including the streamlines that intersected the ROI masks for the precentral gyrus and thalamus.
this case of medically refractory ET treated with MRgFUS and
subsequently DBS to retrospectively evaluate the topography and
fiber tracts modulated in both procedures in order to understand
their differential efficacy and side-effect profile. Importantly,
the MRgFUS lesion in this case was not optimized due to
aborting the procedure. However, we feel optimizing targeting
based on reports such as this may prevent future MRgFUS
treatment failures.
Our technique of comparing the overlap in the lesion/VAT
module volume with patient-specific tracts suggested the
difference in treatment outcomes may be explained in part by
the DBS VAT. The MRgFUS lesion was located ventromedially
to the VAT (Figure 4), and was also significantly smaller,
comprising roughly 10% of the volume of the VAT. The MRgFUS
lesion was placed medially to avoid heat extending into the
internal capsule, and thus sonications were moved serially
more medially as the procedure continued to avoid heating of
the pyramidal tract. DBS electrodes were placed in a similar
trajectory, with the most distal contact (contact 0) bordering the
lesion location. During programming, the patient received the
most tremor suppression when contact 2 was activated, moving
the VAT dorsolaterally.
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FIGURE 4 | Bilateral DBS (left hemisphere on right side, right hemisphere on left side) 3D lead reconstruction and VAT generation in LEAD-DBS. DBS electrode
contact spacing models design of Medtronic 3389. The dashes represent the directionality of the induced electric field from the activated contact, in this case
contact 2. The lesion and VAT are localized alongside the internal and external segments of the VIM (VIM-i and VIM-e, respectively) defined by the DISTAL atlas.
Although the tractography findings suggest that more accurate
targeting and larger VAT resulted in more sustained tremor relief,
our case also adds to a further body of evidence about the variable
efficacy of MRgFUS thalamotomy. It is noteworthy that despite
suboptimal targeting and premature cessation of sonications due
to dysarthria, the initial MRgFUS treatment resulted in tremor
relief, albeit temporarily. The onset of tremor recurrence within
1 year postoperatively has been reported in numerous cases in the
literature, even without lesions complicated by dysarthria (Wang
et al., 2018;Halpern et al., 2019). This suggests several plausible
explanations for loss of tremor suppression efficacy over time
after MRgFUS. First, the lesion created may have a penumbra
region of edemanous brain where reversible neuromodulatory
rather than neuroablative effects predominate. Additionally,
ongoing pathologic remodeling occurring among Purkinje and
other cell types in the cerebello-thalamic tremor circuit may lead
to progressive worsening of tremor (Louis and Faust, 2020) in
the face of a well-targeted MRgFUS lesion. Further investigation
should be conducted on the time course of cellular mechanisms
of thalamic MRgFUS lesions in tremor model systems as well as
neuroimaging studies to uncover predictive imaging biomarkers
for tremor recurrence.
Additionally, our tractography analysis here investigates a
single patient’s structural connectivity, but insight can be drawn
into the differences in streamline counts within the DRTT and
CTT, which have been reported to be necessary when using
tractography to define patient-specific neuromodulatory targets
for ET (Coenen et al., 2014). The negligible difference in the
proportion of DRTT streamlines modulated by MRgFUS and
DBS indicates that both modalities targeted this tract in a
similar way, although a different location within the DRTT
was modulated in each procedure. However, when comparing
DBS stimulation to MRgFUS, we found a large increase in the
proportion of CTT streamlines residing within the DBS VAT,
compared to those found within the patient’s MRgFUS lesion
volume. Although prior work has shown that disruption of
cerebellar input into the ventral thalamus is necessary to disrupt
tremor pathophysiology (Gallay et al., 2016), the pattern suggests
that targeting the DRTT alone may not be sufficient, thus future
investigations should explore the role of modulating the CTT to
maintain clinical effectiveness of tremor relief and balancing the
use of imaging to guide targets with intra-procedural findings.
This is in line with findings by Tian et al., which report that the
most efficacious target, in a cohort of ET patients who received
MRgFUS thalamotomy, encompassed both the CTT and DRTT
(Coenen et al., 2014).
Our findings demonstrate modeling white-matter fiber tracts
using probabilistic tractography may serve as a method to inform
and optimize targeting of initial MRgFUS lesions and tailor
rescue procedures for those with recurrent or persistent tremor.
We have demonstrated that the larger size of the DBS VAT,
compared to the MRgFUS lesion, incorporates a larger area of
white-matter to be targeted, allowing for the inclusion of more
fibers of the CTT, as it has been reported that the size of the
lesion is positively correlated to improved treatment outcome
(Federau et al., 2018).
Dysarthria is a common adverse effect of neuromodulatory
procedures targeting the VIM, including both MRgFUS and
DBS. While every attempt is made to mitigate this effect across
procedural modalities, indirect targeting of VIM lends itself to
suboptimal accuracy of sonications and DBS lead placement.
This effect may be caused by stimulation or sonications of the
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Saluja et al. DBS Rescues MRgFUS for ET
posterior limb of the internal capsule. Activation of ventral
contacts in the VIM have also shown to stimulate the homuncular
representation of the head (Montgomery, 2010). Moreover, the
patient’s absence of dysarthria after successful DBS treatment
suggested the dysarthria was due to medial sonications as the
DBS lead was relatively lateral. Using tractography to optimize
targeting is one approach that we highlight in this case study
to attempt to mitigate such troublesome adverse effects. We
believe our case underscores the importance of tractography-
based targeting, which becomes particularly relevant given that
VIM targeting is indirect due to our inability to segment
thalamic nuclei via conventional MRI (Coenen et al., 2014).
There have been reported attempts to directly modulate white-
matter tracts via DBS, such as the DRTT through targeting the
posterior subthalamic area (PSA), which appear to be effective
at suppressing tremor (Dembek et al., 2020). The findings of
our case report further support the idea that indirect VIM
targeting may not be sufficient alone to optimize outcomes for ET
(Benabid et al., 1991). Tractography utilizes the diffusion signal
of the white matter tracts in the brain, which is personalized
to each patient and more directly tells us where to target.
In particular, the canonically activated contacts for VIM DBS
are usually ventrally located (Gallay et al., 2016), but the
most effective contact in our patient was the more superior
contact 2. Moreover, Boutet et al. (2018) have shown that
medially placed lesions in the VIM were associated with 41
times the likelihood of speech adverse effects. Our case report
supports these findings.
A limitation of this work comes from the relatively low spatial
resolution of dMRI at roughly 2 mm isotropic. This indicates
that tractography-based targeting should be used alongside other
targeting methods, such as atlas coregistration, intraoperative
microelectrode recordings, and/or real-time patient examination,
to ensure accurate tract localization. Another limitation includes
that our dMRI acquisitions taken pre-MRgFUS and pre-DBS
had different acquisition parameters. We have accounted for this
difference by comparing the proportion of streamlines targeted
by each method, rather than the raw streamline count, which
may be more affected by varying acquisition parameters. It is
also important to note that in this case, the DRTT was within
the lesional zone of the MRgFUS, and the CTT was additionally
included within the DBS VAT; further investigation should be
conducted to determine the effects of including CTT targeting
by MRgFUS. The findings of this report highlight the need
for prospective validation of tractography-based targeting and
modeling of modulation by lesioning and electrical stimulation
modalities such as DBS.
The datasets generated for this study are available on request to
the corresponding author.
Written informed consent was obtained from the patient for the
publication of this case report.
SS was the main author on this case report. DB, JP, YH, MJ, and
VN helped with data acquisition, analysis, and editing. VS was
the neurologist involved with clinical evaluation and care of the
patient. PG, VS, KP, and JM were involved in the clinical trial for
MRI-guided Focused Ultrasound that our patient was enrolled
in and assisted with the methodologies for data acquisition and
analysis. CH was the neurosurgeon in the clinical trial involved
in the localization of the lesions and assessments post-procedure.
The Supplementary Material for this article can be found
online at:
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distortions in spin-echo echo-planar images: application to diffusion tensor
imaging. Neuroimage 20, 870–888. doi: 10.1016/s1053-8119(03)00336- 7
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Conflict of Interest: PG, VS, and CH did receive percent effort support from
Insightec during the pivotal trial, in which this patient was included.
The remaining authors declare that the research was conducted in the absence of
any commercial or financial relationships that could be construed as a potential
conflict of interest.
Copyright © 2020 Saluja, Barbosa, Parker, Huang, Jensen, Ngo, Santini, Pauly,
Ghanouni, McNab and Halpern. This is an open-access article distributed under the
terms of the Creative Commons Attribution License (CC BY). The use, distribution
or reproduction in other forums is permitted, provided the original author(s) and
the copyright owner(s) are credited and that the original publication in this journal
is cited, in accordance with accepted academic practice. No use, distribution or
reproduction is permitted which does not comply with these terms.
Frontiers in Human Neuroscience | 8June 2020 | Volume 14 | Article 191
... The risk of permanent gait disturbance also needs to be considered in younger ET patients who are unwilling to consent to the risks of DBS. A handful of patients have gone on to have DBS following MRgFUS [15,16], however, in the worst-case scenario, permanent side effects from a MRgFUS treatment may eliminate DBS as a follow on "rescue" therapy. ...
Transcranial MR guided Focused ultrasound (MRgFUS) is a recently approved treatment for patients with Essential Tremor (ET), the commonest movement disorder in clinical practice. In this review, we explain why thalamotomy has returned, how it is performed, and outline the basic eligibility criteria and risks of this procedure. The aim of this article is to provide a practical guide to clinicians seeing ET patients as to what they should consider before referring for this treatment.
... 18 The volume and shape of sonicated tissue likely do not correspond very well with the volume of tissue activation with electrical stimulation during DBS. 19,20,21,22 Still, depending on the patient's skull density ratio and other factors, the focus of the ultrasound energy can be constrained enough to cover a muscle group that is undertreated. Although we know that these initial results must be interpreted with caution and that further validation with more treatment data is needed, we believe that the challenges presented by interpatient variability should not limit further investigation into the use of accelerometers to refine coordinates in an attempt to improve treatment effectiveness. ...
Technical Report
Background: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is used to treat essential tremor and tremor-dominant Parkinson disease. Feedback is collected throughout the procedure to verify the location of the target and completeness of response; however, variability in clinical judgments may underestimate or overestimate treatment response. Objective: To objectively quantify joint motion after each sonication using accelerometers secured to the contralateral upper extremity in an effort to optimize MRgFUS treatment. Methods: Before the procedure, 3 accelerometers were secured to the patient's arm, forearm, and index finger. Throughout the procedure, tremor motion was regularly recorded during postural and kinetic tremor testing and individual joint angle measures were modeled. The joint angle from each accelerometer was compared with baseline measurements to assess changes in angles. Subsequent adjustments to the target location and sonication energy were made at the discretion of the neurosurgeon and neuroradiologist. Results: Intraoperative accelerometer measurements of hand tremor from 18 patients provided quantified data regarding joint angle reduction: 87.3%, 94.2%, and 86.7% for signature writing, spiral drawing, and line drawing tests, respectively. Target adjustment based on accelerometer monitoring of the angle at each joint added substantial value toward achieving optimal tremor reduction. Conclusion: Real-time accelerometer recordings collected during MRgFUS thalamotomy offered objective quantification of changes in joint angle after each sonication, and these findings were consistent with clinical judgments of tremor response. These results suggest that this technique could be used for fine adjustment of the location of sonication energy and number of sonications to consistently achieve optimal tremor reduction.
... Vim is the cerebellum-recipient nucleus of the thalamus and has traditionally been regarded as the preferred target for neuromodulation or lesional neurosurgery to obtain tremor relief (17,18). Growing recent evidences have shown that effectiveness of interventional procedures for tremor may be related to the proximity between the actual Vim lesion and the white matter tracts extending through the Vim, namely the dentato-rubro-thalamic tract (DRTT) (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). Vim ablation would, therefore, interfere with the tremor-sustaining aberrant circuitry (32). ...
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Magnetic Resonance-guided high-intensity Focused Ultrasound (MRgFUS) of the thalamic ventral intermediate nucleus (Vim) for tremor has increasingly gained interest as a new non-invasive alternative to standard neurosurgery. Resting state functional connectivity (rs-FC) correlates of MRgFUS have not been extensively investigated yet. A region of interest (ROI)-to-ROI rs-FC MRI “connectomic” analysis focusing on brain regions relevant for tremor was conducted on 15 tremor-dominant patients with Parkinson's disease who underwent MRgFUS. We tested whether rs-FC between tremor-related areas was modulated by MRgFUS at 1 and 3 months post-operatively, and whether such changes correlated with individual clinical outcomes assessed by the MDS-UPDRS-III sub items for tremor. Significant increase in FC was detected within bilateral primary motor (M1) cortices, as well as between bilateral M1 and crossed primary somatosensory cortices, and also between pallidum and the dentate nucleus of the untreated hemisphere. Correlation between disease duration and FC increase at 3 months was found between the putamen of both cerebral hemispheres and the Lobe VI of both cerebellar hemispheres, as well as between the Lobe VI of untreated cerebellar hemisphere with bilateral supplementary motor area (SMA). Drop-points value of MDS-UPDRS at 3 months correlated with post-treatment decrease in FC, between the anterior cingulate cortex and bilateral SMA, as well as between the Lobe VI of treated cerebellar hemisphere and the interpositus nucleus of untreated cerebellum. Tremor improvement at 3 months, expressed as percentage of intra-subject MDS-UPDRS changes, correlated with FC decrease between bilateral occipital fusiform gyrus and crossed Lobe VI and Vermis VI. Good responders (≥50% of baseline tremor improvement) showed reduced FC between bilateral SMA, between the interpositus nucleus of untreated cerebellum and the Lobe VI of treated cerebellum, as well as between the untreated SMA and the contralateral putamen. Good responders were characterized at baseline by crossed hypoconnectivity between bilateral putamen and M1, as well as between the putamen of the treated hemisphere and the contralateral SMA. We conclude that MRgFUS can effectively modulate brain FC within the tremor network. Such changes are associated with clinical outcome. The shifting mode of integration among the constituents of this network is, therefore, susceptible to external redirection despite the chronic nature of PD.
... In combination with resting-state functional MRI, dMRI has proven successful for investigating cortical and subcortical organization in humans and nonhuman primates (Sallet et al. 2013;Chowdhury et al. 2013). dMRI results have also been used in patients to refine precise targeting of deep brain stimulation or brain lesion sites (Coenen et al. 2014;Saluja et al. 2020). ...
Full-text available
Noninvasive diffusion-weighted magnetic resonance imaging (dMRI) can be used to map the neural connectivity between distinct areas in the intact brain, but the standard resolution achieved fundamentally limits the sensitivity of such maps. We investigated the sensitivity and specificity of high-resolution postmortem dMRI and probabilistic tractography in rhesus macaque brains to produce retinotopic maps of the lateral geniculate nucleus (LGN) and extrastriate cortical visual area V5/MT based on their topographic connections with the previously established functional retinotopic map of primary visual cortex (V1). We also replicated the differential connectivity of magnocellular and parvocellular LGN compartments with V1 across visual field positions. Predicted topographic maps based on dMRI data largely matched the established retinotopy of both LGN and V5/MT. Furthermore, tractography based on in vivo dMRI data from the same macaque brains acquired at standard field strength (3T) yielded comparable topographic maps in many cases. We conclude that tractography based on dMRI is sensitive enough to reveal the intrinsic organization of ordered connections between topographically organized neural structures and their resultant functional organization.
... Direct targeting refers to identifying the desired structure based on direct imaging-based visualization, while indirect targeting refers to the use of stereotactic coordinates [25]. For example, using diffusion tensor imaging tractography to guide MRgFUS for ET, the dentatorubrothalamic (DRT) tract can be directly targeted, while avoiding the pyramidal tract and medial lemniscus, in order to improve clinical effect (tremor reduction) and minimize motor and sensory adverse events, respectively [26,27]. Tractography-based direct targeting is an evolving field that may improve patient outcomes using personalized neurophysiological findings. ...
Full-text available
Introduction Brain lesioning is a fundamental technique in the functional neurosurgery world. It has been investigated for decades and presented promising results long before novel pharmacological agents were introduced to treat movement disorders, psychiatric disorders, pain, and epilepsy. Ablative procedures were replaced by effective drugs during the 1950s and by Deep Brain Stimulation (DBS) in the 1990s as a reversible neuromodulation technique. In the last decade, however, the popularity of brain lesioning has increased again with the introduction of magnetic resonance-guided focused ultrasound (MRgFUS). Objective In this review, we will cover the current and emerging role of MRgFUS in functional neurosurgery. Methods Literature review from PubMed and compilation. Results Investigated since 1930, MRgFUS is a technology enabling targeted energy delivery at the convergence of mechanical sound waves. Based on technological advancements in phased array ultrasound transducers, algorithms accounting for skull penetration by sound waves, and MR imaging for targeting and thermometry, MRgFUS is capable of brain lesioning with sub-millimeter precision and can be used in a variety of clinical indications. Conclusion MRgFUS is a promising technology evolving as a dominant tool in different functional neurosurgery procedures in movement disorders, psychiatric disorders, epilepsy, among others.
Purpose of review: To review the most recent evidence about the clinical applicability of transcranial MRI-guided focused ultrasound (MRgFUS), including clinical evidence and indications, recent technical developments for its use and future prospects. Recent findings: Unilateral MRgFUS thalamotomy for both essential and parkinsonian tremors is an approved and well established therapy. Recent studies have focused on its long-term safety and efficacy as well as technical advances for refining the approach. Moreover, ultrasound has expanded its application in Parkinson's disease, with clinical trials successfully targeting other brain regions like the subthalamic nucleus, the globus pallidus and the pallidothalamic tract, providing benefits for features that thalamotomy neglects. New indications, such as focal dystonia or neuropsychiatric conditions (namely obsessive-compulsive disorder and depression) have also been explored, with encouraging preliminary results. Finally, the application of ultrasound in low-intensity modality allows other approaches like focal blood-brain barrier opening and neuromodulation, which promise to be highly relevant in translational research. Summary: MRgFUS is a growing emergent technique. Its application in clinical routine is becoming widely accepted as a therapeutic option. Novel approaches and new potential applications are anticipated.
High Intensity Focused Ultrasound (HIFU) is an emerging and increasingly useful modality in the treatment of cancer and other diseases. Although traditional use of ultrasound at lower frequencies has primarily been for diagnostic imaging purposes, the development of HIFU has allowed this particular modality to expand into therapeutic use. This non-invasive and acoustic method involves the use of a piezoelectric transducer to deliver high-energy pulses in a spatially coordinated manner, while minimizing damage to tissue outside the target area. This review describes the history of the development of diagnostic and therapeutic ultrasound and explores the biomedical applications utilizing HIFU technology including thermally ablative treatment, therapeutic delivery mechanisms, and neuromodulatory phenomena. The application of HIFU across various tumor types in multiple organ systems is explored in depth, with particular attention to successful models of HIFU in the treatment of various medical conditions. Basic mechanisms, preclinical models, previous clinical use, and ongoing clinical trials are comparatively discussed. Recent advances in HIFU across multiple medical fields reveal the growing importance of this biomedical technology for the care of patients and for the development of possible pathways for the future use of HIFU as a commonplace treatment modality.
We report a 42‐year‐old, left‐handed woman with tremor recurrence after radiofrequency right ventral intermediate nucleus (Vim) thalamotomy for an intractable essential tremor. The recurring tremor of the left hand disappeared on conducting magnetic resonance imaging‐guided focused ultrasound (MRgFUS) right Vim thalamotomy based on diffusion tensor imaging (DTI). Referring the location of rubro‐thalamic‐cortical tract, we set the target medial to the prior lesion. Pre‐treatment evaluation with DTI could be important for an accurate targeting and a better outcome. Furthermore, MRgFUS Vim thalamotomy could become one of the options for tremor recurrence after surgical intervention.
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Objective : To investigate the relation between deep brain stimulation (DBS) of the posterior-subthalamic-area (PSA) and the ventral-intermediate-nucleus (VIM) and the distance to the dentatorubrothalamic tract (DRTT) in essential tremor (ET). Methods : Tremor rating scale (TRS) hemi-scores were analyzed in 13 ET patients, stimulated in both the VIM and the PSA in a randomized, crossover trial. Distances of PSA and VIM contacts to population-based DRTTs were calculated. The relationships between distance to DRTT and stimulation amplitude, as well as DBS efficiency (TRS improvement per amplitude) were investigated. Results : PSA contacts were closer to the DRTT (p=0.019) and led to a greater improvement in TRS hemi-scores (p=0.005) than VIM contacts. Proximity to the DRTT was related to lower amplitudes (p<0.001) and higher DBS efficiency (p=0.017). Conclusions : Differences in tremor outcome and stimulation parameters between contacts in the PSA and the VIM can be explained by their different distance to the DRTT.
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Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is a novel and minimally invasive ablative treatment for essential tremor. The size and location of therapeutic lesions producing the optimal clinical benefits while minimizing adverse effects are not known. We examined these relationships in patients with essential tremor undergoing MRgFUS. We studied 66 patients with essential tremor who underwent MRgFUS between 2012 and 2017. We assessed the Clinical Rating Scale for Tremor (CRST) scores at 3 months after the procedure and tracked the adverse effects (sensory, motor, speech, gait, and dysmetria) 1 day (acute) and 3 months after the procedure. Clinical data associated with the postoperative Day 1 lesions were used to correlate the size and location of lesions with tremor benefit and acute adverse effects. Diffusion-weighted imaging was used to assess whether acute adverse effects were related to lesions encroaching on nearby major white matter tracts (medial lemniscus, pyramidal, and dentato-rubro-thalamic). The area of optimal tremor response at 3 months after the procedure was identified at the posterior portion of the ventral intermediate nucleus. Lesions extending beyond the posterior region of the ventral intermediate nucleus and lateral to the lateral thalamic border were associated with increased risk of acute adverse sensory and motor effects, respectively. Acute adverse effects on gait and dysmetria occurred with lesions inferolateral to the thalamus. Lesions inferolateral to the thalamus or medial to the ventral intermediate nucleus were also associated with acute adverse speech effects. Diffusion-weighted imaging revealed that lesions associated with adverse sensory and gait/dysmetria effects compromised the medial lemniscus and dentato-rubro-thalamic tracts, respectively. Lesions associated with adverse motor and speech effects encroached on the pyramidal tract. Lesions larger than 170 mm3 were associated with an increased risk of acute adverse effects. Tremor improvement and acute adverse effects of MRgFUS for essential tremor are highly dependent on the location and size of lesions. These novel findings could refine current MRgFUS treatment planning and targeting, thereby improving clinical outcomes in patients.
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Deep brain stimulation (DBS) is a highly efficacious treatment option for movement disorders and a growing number of other indications are investigated in clinical trials. To ensure optimal treatment outcome, exact electrode placement is required. Moreover, to analyze the relationship between electrode location and clinical results, a precise reconstruction of electrode placement is required, posing specific challenges to the field of neuroimaging. Since 2014 the open source toolbox Lead-DBS is available, which aims at facilitating this process. The tool has since become a popular platform for DBS imaging. With support of a broad community of researchers worldwide, methods have been continuously updated and complemented by new tools for tasks such as multispectral nonlinear registration, structural / functional connectivity analyses, brain shift correction, reconstruction of microelectrode recordings and orientation detection of segmented DBS leads. The rapid development and emergence of these methods in DBS data analysis require us to revisit and revise the pipelines introduced in the original methods publication. Here we demonstrate the updated DBS and connectome pipelines of Lead-DBS using a single patient example with state-of-the-art high-field imaging as well as a retrospective cohort of patients scanned in a typical clinical setting at 1.5T. Imaging data of the 3T example patient is co-registered using five algorithms and nonlinearly warped into template space using ten approaches for comparative purposes. After reconstruction of DBS electrodes (which is possible using three methods and a specific refinement tool), the volume of tissue activated is calculated for two DBS settings using four distinct models and various parameters. Finally, four whole-brain tractography algorithms are applied to the patient‘s preoperative diffusion MRI data and structural as well as functional connectivity between the stimulation volume and other brain areas are estimated using a total of eight approaches and datasets. In addition, we demonstrate impact of selected preprocessing strategies on the retrospective sample of 51 PD patients. We compare the amount of variance in clinical improvement that can be explained by the computer model depending on the method of choice. This work represents a multi-institutional collaborative effort to develop a comprehensive, open source pipeline for DBS imaging and connectomics, which has already empowered several studies, and may facilitate a variety of future studies in the field.
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Purpose To evaluate the use of diffusion magnetic resonance imaging (MRI) tractography for neurosurgical guidance of transcranial MRI-guided focused ultrasound (tcMRgFUS) thalamotomy for essential tremor (ET). Materials and methods Eight patients with medication-refractory ET were treated with tcMRgFUS targeting the ventral intermediate nucleus (Vim) of the thalamus contralateral to their dominant hand. Diffusion and structural MRI data and clinical evaluations were acquired pre-treatment and post-treatment. To identify the optimal target location, tractography was performed on pre-treatment diffusion MRI data between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus. The tractography-identified locations were compared to the lesion location delineated on 1 year post-treatment T2-weighted MR image. Their overlap was correlated with the clinical outcomes measured by the percentage change of the Clinical Rating Scale for Tremor scores acquired pre-treatment, as well as 1 month, 3 months, 6 months and 1 year post-treatment. Results The probabilistic tractography was consistent from subject-to-subject and followed the expected anatomy of the thalamocortical radiation and the dentatothalamic tract. Higher overlap between the tractography-identified location and the tcMRgFUS treatment-induced lesion highly correlated with better treatment outcome (r = −0.929, −0.75, −0.643, p = 0.00675, 0.0663, 0.139 for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex, the entire ipsilateral motor cortex and the contralateral dentate nucleus, respectively, at 1 year post-treatment). The correlation for the tractography between the treated thalamus and the hand-knob region of the ipsilateral motor cortex is the highest for all time points (r = −0.719, −0.976, −0.707, −0.929, p = 0.0519, 0.000397, 0.0595, 0.00675 at 1 month, 3 months, 6 months and 1 year post-treatment, respectively). Conclusion Our data support the use of diffusion tractography as a complementary approach to current targeting methods for tcMRgFUS thalamotomy.
Essential tremor (ET) is the most common tremor disorder globally and is characterized by kinetic tremor of the upper limbs, although other clinical features can also occur. Postmortem studies are a particularly important avenue for advancing our understanding of the pathogenesis of ET; however, until recently, the number of such studies has been limited. Several recent postmortem studies have made important contributions to our understanding of the pathological changes that take place in ET. These studies identified abnormalities in the cerebellum, which primarily affected Purkinje cells (PCs), basket cells and climbing fibres, in individuals with ET. We suggest that some of these pathological changes (for example, focal PC axonal swellings, swellings in and regression of the PC dendritic arbor and PC death) are likely to be primary and degenerative. By contrast, other changes, such as an increase in PC recurrent axonal collateral formation and hypertrophy of GABAergic basket cell axonal processes, could be compensatory responses to restore cerebellar GABAergic tone and cerebellar cortical inhibitory efficacy. Such compensatory responses are likely to be insufficient, enabling the disease to progress. Here, we review the results of recent postmortem studies of ET and attempt to place these findings into an anatomical–physiological disease model.
Objective: To test the hypothesis that transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is effective, durable, and safe for patients with medication-refractory essential tremor (ET), we assessed clinical outcomes at 3-year follow-up of a controlled multicenter prospective trial. Methods: Outcomes were based on the Clinical Rating Scale for Tremor, including hand combined tremor-motor (scale of 0-32), functional disability (scale of 0-32), and postural tremor (scale of 0-4) scores, and total scores from the Quality of Life in Essential Tremor Questionnaire (scale of 0-100). Scores at 36 months were compared with baseline and at 6 months after treatment to assess for efficacy and durability. Adverse events were also reported. Results: Measured scores remained improved from baseline to 36 months (all p < 0.0001). Range of improvement from baseline was 38%-50% in hand tremor, 43%-56% in disability, 50%-75% in postural tremor, and 27%-42% in quality of life. When compared to scores at 6 months, median scores increased for hand tremor (95% confidence interval [CI] 0-2, p = 0.0098) and disability (95% CI 1-4, p = 0.0001). During the third follow-up year, all previously noted adverse events remained mild or moderate, none worsened, 2 resolved, and no new adverse events occurred. Conclusions: Results at 3 years after unilateral tcMRgFUS thalamotomy for ET show continued benefit, and no progressive or delayed complications. Patients may experience mild degradation in some treatment metrics by 3 years, though improvement from baseline remains significant. Clinicaltrialsgov identifier: NCT01827904. Classification of evidence: This study provides Class IV evidence that for patients with severe ET, unilateral tcMRgFUS thalamotomy provides durable benefit after 3 years.
An 86-year-old right-handed man with medically refractory essential tremor was treated using left-sided MRI-guided focused ultrasound (MRgFUS) thalamotomy targeting the dentatorubrothalamic tract (DRTT) at its intersection with the ventral intermediate nucleus of the thalamus, with immediate symptomatic improvement and immediate postprocedure imaging demonstrating disruption of the DRTT. The patient experienced a partial return of symptoms 9 weeks following the procedure, and MRI demonstrated retraction of the left thalamic ablation site. The patient underwent repeat left-sided MRgFUS thalamotomy 4 months after initial treatment, resulting in reduced tremor. MR thermometry temperature measurements during the second MRgFUS procedure were unreliable with large fluctuations and false readings, likely due to susceptibility effects from the initial MRgFUS procedure. Final sonications were therefore monitored using the amount of energy delivered. The patient fared well after the second procedure and had sustained improvement in tremor control at the 12-month follow-up. This is the first report to describe the technical challenges of repeat MRgFUS with serial imaging.
BACKGROUND Modern robotic-assist surgical systems have revolutionized stereotaxy for a variety of procedures by increasing operative efficiency while preserving and even improving accuracy and safety. However, experience with robotic systems in deep brain stimulation (DBS) surgery is scarce. OBJECTIVE To present an initial series of DBS surgery performed utilizing a frameless robotic solution for image-guided stereotaxy, and report on operative efficiency, stereotactic accuracy, and complications. METHODS This study included the initial 20 consecutive patients undergoing bilateral robot-assisted DBS. The prior 20 nonrobotic, frameless cohort of DBS cases was sampled as a baseline historic control. For both cohorts, patient demographic and clinical data were collected including postoperative complications. Intraoperative duration and number of Microelectrode recording (MER) and final lead passes were recorded. For the robot-assisted cohort, 2D radial errors were calculated. RESULTS Mean case times (total operating room, anesthesia, and operative times) were all significantly decreased in the robot-assisted cohort (all P-values < .02) compared to frameless DBS. When looking at trends in case times, operative efficiency improved over time in the robot-assisted cohort across all time assessment points. Mean radial error in the robot-assisted cohort was 1.40 ± 0.11 mm, and mean depth error was 1.05 ± 0.18 mm. There was a significant decrease in the average number of MER passes in the robot-assisted cohort (1.05) compared to the nonrobotic cohort (1.45, P < .001). CONCLUSION This is the first report of application of frameless robotic-assistance with the Mazor Renaissance platform (Mazor Robotics Ltd, Caesarea, Israel) for DBS surgery, and our findings reveal that an initial experience is safe and can have a positive impact on operative efficiency, accuracy, and safety.
Background: A recent randomized controlled trial investigating unilateral MRI-guided focused ultrasound (FUS) for essential tremor demonstrated efficacy. The long-term durability of this thalamotomy, however, is unknown. Furthermore, the feasibility of stimulating a previously lesioned target such as the thalamic nucleus ventralis intermedius (Vim) is poorly understood. We report a case of tremor recurrence, following an initially successful FUS thalamotomy, in which Vim-DBS was subsequently utilized to regain tremor control. Methods: An 81-year-old right-handed female with medically refractory essential tremor (a Clinical Rating Scale for Tremor [CRST] value of 73) underwent left-sided FUS thalamotomy with initial abolition of right-upper extremity tremor. By the 6-month follow-up, there was complete recurrence of tremor (a CRST value of 76). The patient subsequently underwent left-sided Vim-DBS. Results: Vim-DBS provided clinical improvement with a CRST value of 42 at the 3-month follow-up; the patient continues to do clinically well at the 6-month follow-up. This result mirrors previous reported cases of stimulation following radiofrequency and gamma-knife lesioning. Our literature review highlights several reasons for the waning of clinical benefit seen with lesional procedures. Conclusion: This case demonstrates that thalamic DBS can salvage a failed FUS thalamotomy and also the feasibility of stimulating a previously lesioned target.
Objective: Magnetic resonance guided focused ultrasound (MRgFUS) has recently been investigated as a new treatment modality for essential tremor (ET), but the durability of the procedure has not yet been evaluated. This study reports results at a 2- year follow-up after MRgFUS thalamotomy for ET. Methods: A total of 76 patients with moderate-to-severe ET, who had not responded to at least two trials of medical therapy, were enrolled in the original randomized study of unilateral thalamotomy and evaluated using the clinical rating scale for tremor. Sixty-seven of the patients continued in the open-label extension phase of the study with monitoring for 2 years. Nine patients were excluded by two years, for example because of alternative therapy such as deep brain stimulation (n = 3) or inadequate thermal lesioning (n = 1). However, all patients in each follow-up period were analyzed. Results: Mean hand tremor score at baseline (19.8±4.9, 76 patients) improved by 55% at 6 months (8.6±4.5, 75 patients). The improvement in tremor score from baseline was durable at 1 year (53%, 8.9±4.8, 70 patients) and at 2 years (56%, 8.8±5.0, 67 patients). Similarly, the disability score at baseline (16.4±4.5, 76 patients) improved by 64% at 6 months (5.4±4.7, 75 patients). This improvement was also sustained at 1 year (5.4±5.3, 70 patients) and at 2 years (6.5±5.0, 67 patients). Paresthesias and gait disturbances were the most common adverse effects at 1 year-each observed in 10 patients with an additional 5 patients experiencing neurological adverse effects. None of the adverse events worsened over the period of follow up and 2 of these resolved. There were no new delayed complications at 2 years. Interpretation: Tremor suppression after MRgFUS thalamotomy for ET is stably maintained at 2 years. Latent or delayed complications do not develop after treatment. This article is protected by copyright. All rights reserved.