Introduction: MRI-guided focused ultrasound (FUS) is an incisionless thermo-ablative procedure that may be used to treat medication-refractory movement disorders, with a growing number of potential anatomic targets and clinical applications. As of this article’s publication, the only US Food and Drug Administration (FDA)-approved uses of FUS for movement disorders are thalamotomy for essential tremor (ET) and tremor-dominant Parkinson’s Disease (PD), and pallidotomy for other cardinal symptoms of PD. We present a state-of-the-art review on all non-FDA approved indications of FUS for movement disorders, beyond the most well-described indications of ET and PD. Our objective was to summarize the safety and efficacy of FUS in this setting and provide a roadmap for future directions of FUS for movement disorders. Methods: A state-of-the-art review was conducted on use of FUS for non-FDA approved movement disorders. All movement disorders excluding FDA-approved uses for ET and PD were included. Results: A total of 25 studies on 172 patients were included. In patients with tremor plus dystonia syndromes (n = 6), ventralis intermediate nucleus of the thalamus (VIM)-FUS gave >50% tremor reduction, with no improvement in dystonia and worsened dystonia in 2/6 patients. Ventral-oralis complex (VO)-FUS gave >50% improvement for focal hand dystonia (n = 6) and 100% return to musical performance in musician’s dystonia (n = 6). In patients with multiple sclerosis (MS) and tremor (n = 3), improvement in tremor was seen in 2 patients with a favorable skull density ratio; no MS disease change was noted after VIM-FUS. In patients with tremor and comorbid ataxia syndromes (n = 3), none were found to have worsened ataxia after VIM-FUS; all had clinically significant tremor improvement. Subthalamic nucleus (STN)-FUS for PD (n = 49) gave approximately 50% improvement in PD motor symptoms, with dystonia and mild dyskinesias as possible adverse effects. Cerebellothalamic tract (CTT-FUS) for ET (n = 42) gave 55–90% tremor improvement, with gait dysfunction as a rare persistent adverse effect. Pallidothalamic tract (PTT-FUS) for PD (n = 50) gave approximately 50% improvement in motor symptoms, with mild speech dysfunction as a possible adverse effect. Conclusion: VIM-FUS appeared safe and effective for heterogenous tremor etiologies, and VO-FUS appeared most effective for isolated segmental dystonia. STN-FUS was effective for PD symptom reduction; postoperative dystonia and mild on-medication dyskinesias required medical management. Tractography-based targeting with CTT-FUS for ET and PTT-FUS for PD demonstrated promising early results. Larger prospective trials with long-term follow-up are needed to the evaluate the safety and efficacy non-FDA approved indications for FUS.

1.
Elias
WJ
,
Lipsman
N
,
Ondo
WG
,
Ghanouni
P
,
Kim
YG
,
Lee
W
, et al
.
A randomized trial of focused ultrasound thalamotomy for essential tremor
.
N Engl J Med
.
2016
;
375
(
8
):
730
9
. .
2.
Krishna
V
,
Fishman
PS
,
Eisenberg
HM
,
Kaplitt
M
,
Baltuch
G
,
Chang
JW
, et al
.
Trial of globus pallidus focused ultrasound ablation in Parkinson’s disease
.
N Engl J Med
.
2023
;
388
(
8
):
683
93
. .
3.
Horisawa
S
,
Yamaguchi
T
,
Abe
K
,
Hori
H
,
Fukui
A
,
Iijima
M
, et al
.
Magnetic resonance-guided focused ultrasound thalamotomy for focal hand dystonia: a pilot study
.
Mov Disord
.
2021
;
36
(
8
):
1955
9
. .
4.
Purrer
V
,
Upadhyay
N
,
Pieper
CC
,
Klockgether
T
,
Boecker
H
,
Wüllner
U
, et al
.
Magnetic resonance imaging-guided focused ultrasound thalamotomy in spinocerebellar ataxia type 12
.
Mov Disord
.
2022
;
37
(
4
):
872
3
. .
5.
Lennon
JC
,
Hassan
I
.
Magnetic resonance-guided focused ultrasound for Parkinson’s disease since ExAblate, 2016–2019: a systematic review
.
Neurol Sci
.
2021
;
42
(
2
):
553
63
. .
6.
Fasano
A
,
Sammartino
F
,
Llinas
M
,
Lozano
AM
.
MRI-guided focused ultrasound thalamotomy in fragile X–associated tremor/ataxia syndrome
.
Neurology
.
2016
;
87
(
7
):
736
8
. .
7.
Cerquera
C
,
Rumià
J
,
Herrera
JM
,
Moreno
V
,
Bargalló
N
,
Valldeoriola
F
.
A single case report of MR-guided focused ultrasound thalamotomy for tremor in fragile X-associated tremor/ataxia
.
Parkinsonism Relat Disord
.
2016
;
28
:
159
60
. .
8.
Máñez-Miró
JU
,
Martínez-Fernández
R
,
Del Alamo
M
,
Pineda-Pardo
JA
,
Fernández-Rodríguez
B
,
Alonso-Frech
F
, et al
.
Focused ultrasound thalamotomy for multiple sclerosis-associated tremor
.
Mult Scler
.
2020
;
26
(
7
):
855
8
. .
9.
Gagliardo
C
,
Ragonese
P
,
Iacopino
GD
,
Salemi
G
,
Midiri
M
,
D’Amelio
M
.
Transcranial magnetic resonance-guided focused ultrasound thalamotomy as a safe treatment option in multiple sclerosis patients with essential tremor
.
Neurol Sci
.
2021
;
42
(
3
):
1139
43
. .
10.
Jackson
LM
,
Kaufmann
TJ
,
Lehman
VT
,
Lee
KH
,
Miller
KJ
,
Hassan
A
, et al
.
Clinical characteristics of patients with gait instability after MR-guided focused ultrasound thalamotomy
.
Tremor Other Hyperkinet Mov
.
2021
;
11
:
41
. .
11.
Levi
V
,
Eleopra
R
,
Franzini
A
,
Romito
L
.
Is Deep Brain Stimulation still an option for tremor recurrence after Focused Ultrasound thalamotomy? A case report
.
J Clin Neurosci
.
2019
;
68
:
344
6
. .
12.
Maesawa
S
,
Torii
J
,
Nakatsubo
D
,
Noda
H
,
Mutoh
M
,
Ito
Y
, et al
.
A case report: dual-lead deep brain stimulation of the posterior subthalamic area and the thalamus was effective for Holmes tremor after unsuccessful focused ultrasound thalamotomy
.
Front Hum Neurosci
.
2022
;
16
:
1065459
. .
13.
Martino
D
,
Rockel
CP
,
Bruno
V
,
Mazerolle
EL
,
Jetha
S
,
Pichardo
S
, et al
.
Dystonia following thalamic neurosurgery: a single centre experience with MR-guided focused ultrasound thalamotomy
.
Parkinsonism Relat Disord
.
2020
;
71
:
1
3
. .
14.
Fasano
A
,
Llinas
M
,
Munhoz
RP
,
Hlasny
E
,
Kucharczyk
W
,
Lozano
AM
.
MRI-guided focused ultrasound thalamotomy in non-ET tremor syndromes
.
Neurology
.
2017
;
89
(
8
):
771
5
. .
15.
Meng
Y
,
Suppiah
S
,
Scantlebury
N
,
Lipsman
N
,
Schwartz
ML
.
Treatment of a patient with task-specific writing tremor using magnetic resonance-guided focused ultrasound
.
Can J Neurol Sci
.
2018
;
45
(
4
):
474
7
. .
16.
Horisawa
S
,
Yamaguchi
T
,
Abe
K
,
Hori
H
,
Sumi
M
,
Konishi
Y
, et al
.
A single case of MRI-guided focused ultrasound ventro-oral thalamotomy for musician’s dystonia
.
J Neurosurg
.
2018
;
131
(
2
):
384
6
. .
17.
Jamora
RDG
,
Chang
WC
,
Taira
T
.
Transcranial magnetic resonance-guided focused ultrasound in X-linked dystonia-parkinsonism
.
Life
.
2021
;
11
(
5
):
392
. .
18.
Martínez-Fernández
R
,
Rodríguez-Rojas
R
,
Del Álamo
M
,
Hernández-Fernández
F
,
Pineda-Pardo
JA
,
Dileone
M
, et al
.
Focused ultrasound subthalamotomy in patients with asymmetric Parkinson’s disease: a pilot study
.
Lancet Neurol
.
2018
;
17
(
1
):
54
63
. .
19.
Martínez-Fernández
R
,
Máñez-Miró
JU
,
Rodríguez-Rojas
R
,
Del Álamo
M
,
Shah
BB
,
Hernández-Fernández
F
, et al
.
Randomized trial of focused ultrasound subthalamotomy for Parkinson’s disease
.
N Engl J Med
.
2020
;
383
(
26
):
2501
13
. .
20.
Martínez-Fernández
R
,
Natera-Villalba
E
,
Máñez Miró
JU
,
Rodriguez-Rojas
R
,
Marta Del Álamo
M
,
Pineda-Pardo
, et al
.
Prospective long-term follow-up of focused ultrasound unilateral subthalamotomy for Parkinson disease
.
Neurology
.
2023
;
100
(
13
):
e1395
405
. .
21.
Fernández
RM
,
Villalba
EN
,
Rodriguez-Rojas
R
, et al
.
Unilateral focused ultrasound subthalamotomy in early Parkinson’s disease: a pilot study
.
J Neurol Neurosurg Psychiatry
.
2023
:
jnnp-2023
331211
. .
22.
Schreglmann
SR
,
Bauer
R
,
Hägele-Link
S
,
Bhatia
KP
,
Natchev
P
,
Wegener
N
, et al
.
Unilateral cerebellothalamic tract ablation in essential tremor by MRI-guided focused ultrasound
.
Neurology
.
2017
;
88
(
14
):
1329
33
. .
23.
Chazen
JL
,
Sarva
H
,
Stieg
PE
,
Min
RJ
,
Ballon
DJ
,
Pryor
KO
, et al
.
Clinical improvement associated with targeted interruption of the cerebellothalamic tract following MR-guided focused ultrasound for essential tremor
.
J Neurosurg
.
2018
;
129
(
2
):
315
23
. .
24.
Gallay
MN
,
Moser
D
,
Rossi
F
,
Pourtehrani
P
,
Magara
AE
,
Kowalski
M
, et al
.
Incisionless transcranial MR-guided focused ultrasound in essential tremor: cerebellothalamic tractotomy
.
J Ther Ultrasound
.
2016
;
4
:
5
. .
25.
Gallay
MN
,
Moser
D
,
Jeanmonod
D
.
MR-guided focused ultrasound cerebellothalamic tractotomy for chronic therapy-resistant essential tremor: anatomical target reappraisal and clinical results
.
J Neurosurg
.
2020
;
134
(
2
):
376
85
. .
26.
Yang
AI
,
Chaibainou
H
,
Wang
S
,
Hitti
FL
,
McShane
BJ
,
Tilden
D
, et al
.
Focused ultrasound thalamotomy for essential tremor in the setting of a ventricular shunt: technical report
.
Oper Neurosurg
.
2019
;
17
(
4
):
376
81
. .
27.
Gallay
MN
,
Moser
D
,
Rossi
F
,
Magara
AE
,
Strasser
M
,
Bühler
R
, et al
.
MRgFUS pallidothalamic tractotomy for chronic therapy-resistant Parkinson’s disease in 51 consecutive patients: single center experience
.
Front Surg
.
2019
;
6
:
76
. .
28.
Chen
JC
,
Lu
MK
,
Chen
CM
,
Tsai
CH
.
Stepwise dual-target magnetic resonance–guided focused ultrasound in tremor-dominant Parkinson disease: a feasibility study
.
World Neurosurg
.
2023
;
171
:
e464
70
. .
29.
Najdenovska
E
,
Tuleasca
C
,
Jorge
J
,
Maeder
P
,
Marques
JP
,
Roine
T
, et al
.
Comparison of MRI-based automated segmentation methods and functional neurosurgery targeting with direct visualization of the Ventro-intermediate thalamic nucleus at 7T
.
Sci Rep
.
2019
;
9
(
1
):
1119
. .
30.
Schaltenbrand
G
,
Walker
AE
.
Stereotaxy of the human brain: anatomical, physiological and clinical applications
.
Georg Thieme
;
1982
.
31.
Molnar
GF
,
Pilliar
A
,
Lozano
AM
,
Dostrovsky
JO
.
Differences in neuronal firing rates in pallidal and cerebellar receiving areas of thalamus in patients with Parkinson’s disease, essential tremor, and pain
.
J Neurophysiol
.
2005
;
93
(
6
):
3094
101
. .
32.
Loeffler
MA
,
Synofzik
M
,
Cebi
I
,
Klocke
,
P
,
Hormozi
,
M
,
Gasser
,
T
, et al
.
Case Report: deep brain stimulation improves tremor in FGF-14 associated spinocerebellar ataxia
.
Front Neurol
.
2022
;
13
:
1048530
. .
33.
Oyama
G
,
Thompson
A
,
Foote
KD
,
Limotai
N
,
Abd-El-Barr
M
,
Maling
N
, et al
.
Deep brain stimulation for tremor associated with underlying ataxia syndromes: a case series and discussion of issues
.
Tremor Other Hyperkinet Mov (N Y)
.
2014
;
4
:
228
. .
34.
Mehanna
R
,
Itin
I
.
Which approach is better: bilateral versus unilateral thalamic deep brain stimulation in patients with fragile X–associated tremor ataxia syndrome
.
Cerebellum
.
2014
;
13
(
2
):
222
5
. .
35.
Weiss
D
,
Mielke
C
,
Wächter
T
,
Bender
B
,
Liscic
RM
,
Scholten
M
, et al
.
Long-term outcome of deep brain stimulation in fragile X-associated tremor/ataxia syndrome
.
Parkinsonism Relat Disord
.
2015
;
21
(
3
):
310
3
. .
36.
Cury
RG
,
França
C
,
Duarte
KP
,
Paraguay
I
,
Diniz
JM
,
Cunha
P
, et al
.
Safety and outcomes of dentate nucleus deep brain stimulation for cerebellar ataxia
.
Cerebellum
.
2022
;
21
(
5
):
861
5
. .
37.
Brandmeir
NJ
,
Murray
A
,
Cheyuo
C
,
Ferari
C
,
Rezai
AR
.
Deep brain stimulation for multiple sclerosis tremor: a meta-analysis
.
Neuromodulation
.
2020
;
23
(
4
):
463
8
. .
38.
Luna
G
,
Alping
P
,
Burman
J
,
Fink
K
,
Fogdell-Hahn
A
,
Gunnarsson
M
, et al
.
Infection risks among patients with multiple sclerosis treated with fingolimod, natalizumab, rituximab, and injectable therapies
.
JAMA Neurol
.
2020
;
77
(
2
):
184
91
. .
39.
Parihar
R
,
Alterman
R
,
Papavassiliou
E
,
Tarsy
D
,
Shih
LC
.
Comparison of VIM and STN DBS for parkinsonian resting and postural/action tremor
.
Tremor Other Hyperkinet Mov (N Y)
.
2015
;
5
:
321
. .
40.
Herzog
J
,
Hamel
W
,
Wenzelburger
R
,
Pötter
M
,
Pinsker
MO
,
Bartussek
J
, et al
.
Kinematic analysis of thalamic versus subthalamic neurostimulation in postural and intention tremor
.
Brain
.
2007
;
130
(
Pt 6
):
1608
25
. .
41.
Fan
H
,
Zheng
Z
,
Yin
Z
,
Zhang
J
,
Lu
G
.
Deep brain stimulation treating dystonia: a systematic review of targets, body distributions and etiology classifications
.
Front Hum Neurosci
.
2021
;
15
:
757579
. .
42.
Volkmann
J
,
Wolters
A
,
Kupsch
A
,
Müller
J
,
Kühn
AA
,
Schneider
GH
, et al
.
Pallidal deep brain stimulation in patients with primary generalised or segmental dystonia: 5-year follow-up of a randomised trial
.
Lancet Neurol
.
2012
;
11
(
12
):
1029
38
. .
43.
Moro
E
,
LeReun
C
,
Krauss
JK
,
Albanese
A
,
Lin
JP
,
Walleser Autiero
S
, et al
.
Efficacy of pallidal stimulation in isolated dystonia: a systematic review and meta-analysis
.
Eur J Neurol
.
2017
;
24
(
4
):
552
60
. .
44.
Tsuboi
T
,
Jabarkheel
Z
,
Zeilman
PR
,
Barabas
MJ
,
Foote
KD
,
Okun
MS
, et al
.
Longitudinal follow-up with VIM thalamic deep brain stimulation for dystonic or essential tremor
.
Neurology
.
2020
;
94
(
10
):
e1073
84
. .
45.
Picillo
M
,
Paramanandam
V
,
Morgante
F
,
Algarni
M
,
Olszewska
DA
,
Munhoz
RP
, et al
.
Dystonia as complication of thalamic neurosurgery
.
Parkinsonism Relat Disord
.
2019
;
66
:
232
6
. .
46.
Ostrem
JL
,
San Luciano
M
,
Dodenhoff
KA
,
Ziman
N
,
Markun
LC
,
Racine
CA
, et al
.
Subthalamic nucleus deep brain stimulation in isolated dystonia: a 3-year follow-up study
.
Neurology
.
2017
;
88
(
1
):
25
35
. .
47.
Odekerken
VJJ
,
Boel
JA
,
Schmand
BA
,
de Haan
RJ
,
Figee
M
,
van den Munckhof
P
, et al
.
GPi vs STN deep brain stimulation for Parkinson disease: three-year follow-up
.
Neurology
.
2016
;
86
(
8
):
755
61
. .
48.
Zhang
J
,
Li
J
,
Chen
F
,
Liu
X
,
Jiang
C
,
Hu
X
, et al
.
STN versus GPi deep brain stimulation for dyskinesia improvement in advanced Parkinson’s disease: a meta-analysis of randomized controlled trials
.
Clin Neurol Neurosurg
.
2021
;
201
:
106450
. .
49.
Coenen
VA
,
Sajonz
B
,
Prokop
T
,
Reisert
M
,
Piroth
T
,
Urbach
H
, et al
.
The dentato-rubro-thalamic tract as the potential common deep brain stimulation target for tremor of various origin: an observational case series
.
Acta Neurochir (Wien)
.
2020
;
162
(
5
):
1053
66
. .
50.
Purrer
V
,
Upadhyay
N
,
Borger
V
,
Pieper
CC
,
Kindler
C
,
Grötz
S
, et al
.
Lesions of the cerebello-thalamic tract rather than the ventral intermediate nucleus determine the outcome of focused ultrasound therapy in essential tremor: a 3T and 7T MRI-study
.
Parkinsonism Relat Disord
.
2021
;
91
:
105
8
. .
51.
Pineda-Pardo
JA
,
Martínez-Fernández
R
,
Rodríguez-Rojas
R
,
Del-Alamo
M
,
Hernández
F
,
Foffani
G
, et al
.
Microstructural changes of the dentato-rubro-thalamic tract after transcranial MR guided focused ultrasound ablation of the posteroventral VIM in essential tremor
.
Hum Brain Mapp
.
2019
;
40
(
10
):
2933
42
. .
52.
Agrawal
M
,
Garg
K
,
Samala
R
,
Rajan
R
,
Naik
V
,
Singh
M
.
Outcome and complications of MR guided focused ultrasound for essential tremor: a systematic review and meta-analysis
.
Front Neurol
.
2021
;
12
:
654711
. .
53.
Horisawa
S
,
Fukui
A
,
Yamahata
H
,
Tanaka
Y
,
Kuwano
A
,
Momosaki
O
, et al
.
Unilateral pallidothalamic tractotomy for akinetic-rigid Parkinson’s disease: a prospective open-label study
.
J Neurosurg
.
2021
;
135
(
3
):
799
805
. .
54.
Maier-Hein
KH
,
Neher
PF
,
Houde
JC
,
Côté
MA
,
Garyfallidis
E
,
Zhong
J
, et al
.
The challenge of mapping the human connectome based on diffusion tractography
.
Nat Comm
.
2017
;
8
(
1
):
1349
. .
55.
Acuna
P
,
Supnet-Wells
ML
,
Spencer
NA
,
de Guzman
JK
,
Russo
M
,
Hunt
A
, et al
.
Establishing a natural history of X-linked dystonia parkinsonism
.
Brain Commun
.
2023
;
5
(
3
):
fcad106
. .
56.
InSightec
A
.
Feasibility clinical trial of the magnetic resonance guided focused ultrasound (MRgFUS) for the management of treatment-refractory movement disorders
.
clinicaltrials.gov
;
2022
. https://clinicaltrials.gov/ct2/show/NCT02252380. (Accessed May 23, 2023).
You do not currently have access to this content.