- Open Access
Incisionless transcranial MR-guided focused ultrasound in essential tremor: cerebellothalamic tractotomy
© Gallay et al. 2016
Received: 10 December 2015
Accepted: 8 February 2016
Published: 13 February 2016
Already in the late 1960s and early 1970s, targeting of the “posterior subthalamic area (PSA)” was explored by different functional neurosurgical groups applying the radiofrequency (RF) technique to treat patients suffering from essential tremor (ET). Recent advances in magnetic resonance (MR)-guided focused ultrasound (MRgFUS) technology offer the possibility to perform thermocoagulation of the cerebellothalamic fiber tract in the PSA without brain penetration, allowing a strong reduction of the procedure-related risks and increased accuracy. We describe here the first results of the MRgFUS cerebellothalamic tractotomy (CTT).
Twenty-one consecutive patients suffering from chronic (mean disease duration 29.9 years), therapy-resistant ET were treated with MRgFUS CTT. Three patients received bilateral treatment with a 1-year interval. Primary relief assessment indicators were the Essential Tremor Rating Scale (Fahn, Tolosa, and Marin) (ETRS) taken at follow-up (3 months to 2 years) with accent on the hand function subscores (HF16 for treated hand and HF32 for both hands) and handwriting. The evolution of seven patients with HF32 above 28 points over 32 (group 1) differentiated itself from the others’ (group 2) and was analyzed separately. Global tremor relief estimations were provided by the patients. Lesion reconstruction and measurement of targeting accuracy were done on 2-day post-treatment MR pictures for each CTT lesion.
The mean ETRS score for all patients was 57.6 ± 13.2 at baseline and 25.8 ± 17.6 at 1 year (n = 10). The HF16 score reduction was 92 % in group 2 at 3 months and stayed stable at 1 year (90 %). Group 1 showed only an improvement of 41 % at 3 months and 40 % at 1 year. Nevertheless, two patients of group 1 treated bilaterally had an HF16 score reduction of 75 and 88 % for the dominant hand at 1 year after the second side. The mean patient estimation of global tremor relief after CTT was 92 % at 2 days and 77 % at 1-year follow-up.
CTT with MRgFUS was shown to be an effective and safe approach for patients with therapy-refractory essential tremor, combining neurological function sparing with precise targeting and the possibility to treat patients bilaterally.
Essential tremor (ET) is the most common pathological tremor in humans, frequently undiagnosed, often refractory to conservative treatments, and with the potential to cause severe disability [1–4]. In this context, a neurosurgical option has been considered [5, 6].
Already in the late 1960s and early 1970s, stereotactic targeting of the posterior subthalamic area (PSA) also named prelemniscal radiation or posterior zona incerta was explored worldwide by different functional neurosurgical groups [7–12] to treat ET, as an alternative to the ventral intermediate nucleus thalamotomy (Vim of Hassler, corresponding to the posterior part of the thalamic ventral lateral nucleus (VLp)) [13–16]. VLp thalamotomies were extensively performed from the 1960s to the 1990s [17–26]. The published results of the posterior subthalamic approach, taking into account technical limitations of their time, were highly promising.
We correlate this with the sparing of the thalamocortical network and thus a reduction of neurological motor and cognitive deficits, particularly desirable in the case of bilateral treatments. Such sparing of the thalamus makes all the more sense that the pathology of essential tremor lies in the cerebellar input to the motor thalamus.
There is sound histological evidence that the so-called PSA, also named prelemniscal radiation by Hassler or field H by Forel, includes in fact the cerebellothalamic (or dentato-thalamic) fiber tract on its way to the VLp [14, 46]. The dentato-rubro-thalamic denomination should not be used in humans, as no rubro-thalamic connections have been reported in the literature. The only evidence for such connections was described in the cat , and they were absent in the monkey .
Recent clinicopathological data point to the cerebellar system in ET [2, 49]. Purkinje cell losses and changes in their different cell compartments (dendrites, body, axon, basket cell processes, and climbing fiber-Purkinje connections) have been described, supporting the possibility of reduced inhibition of the dentate nucleus and thus overactivation of the VLp.
The technology of incisionless transcranial magnetic resonance (MR)-guided focused ultrasound (MRgFUS) has already been successfully applied to thalamotomies in chronic neuropathic pain and essential tremor [6, 50–53] and to pallidothalamic tractotomies  in Parkinson’s disease, with a precision inside half a millimeter not obtainable by techniques implying brain penetration [55, 56].
This case series is the first to include patients operated for chronic therapy-refractory ET with MRgFUS CTT. A technical report of the CTT performed with radiofrequency ablation was published by Magnin et al. , and Ledermann et al.  addressed the neuropsychological outcome of this specific procedure.
Characteristics of the 21 patients with means ± SD
Age in years
69.1 ± 9.2
Baseline tremor score on ETRS (0 to 144)
57.6 ± 13.2
Duration of tremor in years
29.9 ± 15.0
Family history of tremor
The patients were seen by neurologists who ascertained the diagnosis and the resistance to drug treatment. They received beta blockers (n = 18), primidone (n = 10), topiramate (n = 3), octanol (n = 1), clonazepam (n = 3), gabapentin (n = 3), modafinil (n = 1), and baclofen (n = 1). They were evaluated by an internist as to contraindications to surgery. No patient took anticoagulant or antiaggregant drugs within 10 days before surgery. Blood workout was performed, and all patients had normal electrolytes and coagulation status.
ET with postural and/or kinetic components reaching an intensity of at least 3 over 4
Tremor resistance to pharmacological treatment or appearance of side effects of drugs preventing their use
Absence of dementia
Strongly diminished quality of life
Preoperative assessment included an Essential Tremor Rating Scale (ETRS) (Fahn, Tolosa, and Marin Tremor Rating Scale) , full neurological status including a video recording, Montreal Cognitive Assessment (MoCA), and Hospital Anxiety and Depression Scale (HADS).
Primary relief assessment indicators were postoperative ETRS, hand function subscore (item 11–14 of ETRS, describing spiral and line drawings and pouring) presented for the targeted hand over 16 points (HF16) and for both hands over 32 points (HF32), handwriting (item 10 of ETRS), drawing of spirals, and estimation of global tremor relief by the patient (in percent). Spirals were drawn with both hands with and without support on table. The worst tremulous spirals were always used in pre- and postoperative scoring of ETRS.
The patients signed an informed consent form after having been fully instructed about the treatment, its results, and risks.
CTT was performed unilaterally in 18 and bilaterally in 3 patients. In bilateral treatments, it was performed first on the left, with a 1-year interval for the second side. In two patients (1 and 2), a complement of targeting was performed on the already operated side during the second treatment session.
Postoperative follow-ups were performed at 3 months and 1 year. For international patients (16 over 21), the 3-month assessment was performed per correspondence with video recordings and drawing of spirals.
Focused ultrasound procedure
The procedures were performed in a 3-T MR imaging system (GE Discovery 750, GE Healthcare, Milwaukee, WI, USA) using the ExAblate Neuro device (InSightec, Haifa, Israel).
Targeting was performed using the stereotactic multiarchitectonic Morel Atlas of the Human Thalamus and Basal Ganglia . Target coordinates of the cerebellothalamic tract were 5.0 mm posterior to the mid-commissural line in the anteroposterior (AP) direction, 8.0 mm lateral to the thalamo-ventricular border in the mediolateral (ML) direction, and 3 mm below the intercommissural plane.
MR imaging was performed for co-registration preoperatively and at day 2 after surgery (Moser et al. 2012, 2013 and Magara et al. 2014) [54–56]. Target reconstruction was performed on the basis of the MR imaging at day 2 after surgery as previously described [55, 56] with comparison between desired target coordinates and coordinates of the geometric center of the lesions seen on the sagittal and axial T2-weighted images. As in Moser et al., targeting accuracy values were given for each of the three dimensions (ML, AP, and dorsoventral (DV)) in millimeters as well as 3D vector accuracy.
Statistical analysis was performed with Microsoft Excel and XL Toolbox for Excel, using t test, regression analysis and Levene’s test of equal variance. Statistical significance was fixed at p < 0.05.
The treatment characteristics include: ETRS, drawing of spirals, handwriting, gait instability, HADS, MoCA and hand function subscores (HF16 and HF32) at baseline (B), 2 days after the procedure (2d), 3 months (3m), and the last follow-up (F) ranging from 1 year (1y) to 2 years (2y) and in percent of improvement (%i)
Gait instability (B/2d/F)
HF16 (2d/1y after the second side/%i)
11/0.6/95 %/1.1/90 %/1.2/90 %
We then set a limit with a preoperative HF32 score more than 28 points over 32, determining a group 1 (n = 7, HF32 > 28/32) and a group 2 (n = 14, HF32 ≤ 28/32). The preoperative HF32 did not pass Levene’s test for equality of variance as well as all postoperative HF16 scores (2 days, 3 months, and 1 year) and the postoperative handwriting scores, whereas the preoperative ETRS and HF16 scores did. This supports at statistical level the separation of groups 1 and 2 as different patient populations on the basis of the preoperative HF32 score. There are age differences between the two groups, which however did not qualify statistically as separator (mean age was 76.4 ± 4.7 in group 1 and 65.5 ± 8.8 in group 2).
The baseline HF16 was 12.4 (SD± 3.3) in both groups, 15.3 (SD± 1.3) in group 1 and 11.0 (SD± 3.1) in group 2. The mean improvement in HF16 at 3 months for both groups was 74 % (41 % for group 1, 90 % for group 2) and 78 % at 1-year follow-up (40 % in group 1 and 90 % for group 2). The two patients in group 1 treated bilaterally showed 75 and 88 % improvement of HF16 in their dominant hand, as well as 78 % and 56 improvement of HF16 in their non-dominant hand 1 year after the treatment of the second side. There was a highly significant effect of CTT on the HF16 score at 2 days, 3 months, and 1 year post-procedure (p < 0.001).
The mean global tremor relief as estimated by the patients was 92 % for the treated hand at 2 days (n = 21) and 77 % at 1 year (n = 12). Head tremor was never the dominant tremor component and was found in six patients with a mean of 1.2 (SD± 0.57) (n = 6) at baseline and 0.25 (SD± 0.2) (n = 6) at 3 months. Preoperative postural tremor was found in 17/21 patients (mean 1.7, SD± 1.2). At the latest follow-up, only one patient showed a postural tremor (1–2 over 4) in the treated upper extremity.
No bleeding occurred. A worsening of pre-existing gait instability was found in five patients, with maximal worsening of 1 point over 4 (mean 0.7/4 ± 0.3). At the last follow-up (3 months to 1 year), only one patient did not fully recover to his original walking ability and was 0.5 points worse than preoperatively. There were no other side effects.
The applied target reconstruction procedure has of course a given measurement inaccuracy. Error sources, each around half a millimeter, are 1) variations of thalamo-ventricular border position due to differences of MR picture windowing, 2) thickness of the MR slices, 3) determination of the centers of the ac and pc, 4) determination of the center of more or less regular ellipsoidal lesions and 5) variable amounts of lesional and perilesional edema.
The results presented here demonstrate a postoperative reduction of the ETRS score comparable to other studies. The mean baseline tremor score was also comparable to others (57.6 ± 13.2/144 versus 49.4/144 ± 15.3 for Blomstedt et al. , 56.8 ± 12.7 in Nazzaro  and 54.9/160 ± 14.4 in Elias ). As discussed in the “Results” section, we present separately the spirals, pre- and postoperative handwritings (item 10 of ETRS), and the HF16, after having separated our patients in groups 1 and 2.
Group 1 comprises patients with severe tremor forms (HF32 > 28/32). To our knowledge, the issue of their postsurgical outcome has not been specifically addressed in the literature. Regression analysis in Blomstedt et al. pointed to severity of tremor before surgery as an important predicting factor for residual tremor. In some group 1 patients, we observed, after a good initial evolution, a recurrent pattern of low-frequency (about 1–2 Hz) dysmetric activity on the operated side disturbing drawing, drinking, and handwriting. These tests were scored up to 4 over 4 but do not indicate exclusively the presence of tremor. In an analysis of our group 2 patients, with at least one item at 3/4 but a total functional hand score of ≤8/32, HF16 score improvement was 90 % (n = 14) at 3 months and 90 % at (n = 9) 1 year. This selected, clearly less affected patient group remains perfectly comparable to other studies (mean ETRS 50.9 ± 8.8 and mean dominant hand score of 11.0/16 ± 3.1 versus 49.4 ± 15.3 and 10.6/16 ± 4.1 for Blomstedt et al. ). The evolution of patients 1 and 2 in group 1 provides evidence for two potential additional factors explaining the resistance of tremor in group 1 patients: they showed strong tremor relief after the second bilateral focused ultrasound treatment comprising a target complementation of the first CTT. This points to a possible deleterious effect of a still overactive untreated hemisphere on the other treated side. In addition, the CTT complementation may indicate the necessity of complete target coverage in the context of a particular strong physiopathology. Thus, patients with severe bilateral ET would need a complete and bi-hemispheric CTT treatment. In addition, some of them display an outspoken telo-diencephalic angiopathic state (status cribrosus) which may have been the cause of a reduced response to sonication.
Bilateral treatment has been performed in three patients, with 1-year delay in each patient between the two sides. There is high evidence through the literature advising against bilateral lesioning in the VLp. Our preliminary results show good tolerance for bilateral subthalamic lesioning of the cerebellothalamic tract, as CTT procedures did not produce side effects apart from a slight worsening (increase of 0.5/4) of pre-existent gait instability, noted in 5 over 21 cases. Only one persisted at 1-year follow-up (2.5/4 compared to 2/4 preoperatively). This specific patient had concomitantly a documented polyneuropathy and a cervical canal stenosis which may well have played a role in this persisting slight gait instability.
Comparison of techniques
There are currently four main surgical options in the treatment of essential tremor: DBS, radiofrequency (RF) lesioning, gamma knife, and newly MRgFUS.
RF lesioning in the VLp is based on a long experience which has shown efficacy and stability over time [17, 19, 20, 22, 23, 26, 61–63]. The rates of neurological deficits in VLp RF lesioning led most of the neurosurgical groups to change their approach over time in favor of DBS. To the present day, VLp RF lesioning is still used in selected situations [64, 65]. Preliminary results of unilateral VLp thalamotomy with focused ultrasound [6, 50, 52] did not show the same extent of adverse events as in RF series, probably due to better lesion control and the incisionless approach. The most common side effects in Elias et al.  were paresthesias.
The DBS approach is currently the most frequently chosen (or at least published) option with high rates of tremor control [5, 27–31, 62, 66–69]. The rate of neurological and hardware-related complications of DBS interventions is however significant in the short and long terms [50, 67, 70–75]. As a typical example from a detailed study, Pahwa et al.  reported 63 % of dysarthria, 38 % of incoordination, 25 % of paresthesia, and 25 % abnormal gait in bilateral chronic VLp stimulation for ET as well as paresthesias in 56 %, incoordination and dysarthria in 17 % in unilateral stimulation.
Gamma knife thalamotomy has been shown to achieve improvement for tremor scores over the long term averaging 50 to 60 % and low rates of permanent neurological deficits [76, 77], which were mostly due to unpredictable excessive radiation reactions. Bilateral treatment did not show any increase in adverse events with this approach . So far, the main advantage of ultrasound technology over gamma knife, apart from using non-ionizing energy, is the direct control over the lesioning process provided by on-line MR thermometry, reversibility at low temperatures, and direct clinical feedback.
Our results profile the targeting of the cerebellothalamic tract in the posterior subthalamic area with focused ultrasound as an efficient, minimally invasive, safe, and hardware-free approach against chronic, therapy-refractory essential tremor, combining neurological function sparing with precise targeting and with the possibility to treat bilaterally.
Beyond the option for a technique modality, which should provide maximal safety and precision, the choice of a target should be based on sound physiopathological evidence. In our opinion, the sparing of the thalamocortical network, in this case its motor part, correlates with reduced neurological deficits and thus the possibility to treat bilaterally. This is the primary issue, which has been addressed first in the sixties with RF subthalamotomies [7, 9, 11] as well as nowadays with PSA DBS [33–45] and MRgFUS (this study). This demonstrates that the historical search for a reduction or suppression of deficits can be solved by a proper target choice and not by a given technology. Recent developments tend to address mostly the technical point of view but not the target choice.
The issue of the severe ET patients who are poor responders to surgery remains to be elucidated by further studies. In those patients, bilateral treatment and complete target coverage seem to be necessary in order to achieve satisfactory tremor relief.
The authors thank Mrs. Tanja Thalmann for intraoperative patient support and monitoring and Dr. Mike Fitze and Dr. Oskar Blosser of Rodiag Diagnostic Centers for MR imaging.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Louis ED. Essential tremor. Lancet Neurol. 2005;4:100–10.View ArticlePubMedGoogle Scholar
- Louis ED. Essential tremor: evolving clinicopathological concepts in an era of intensive post-mortem enquiry. Lancet Neurol. 2010;9:613–22.View ArticlePubMedGoogle Scholar
- Louis ED, Hernandez N, Michalec M. Prevalence and correlates of rest tremor in essential tremor: cross-sectional survey of 831 patients across four distinct cohorts. Eur J Neurol. 2015;6:927–32.View ArticleGoogle Scholar
- Zakaria R, Lenz FA, Hua S, Avin BH, Liu CC, Mari Z. Thalamic physiology of intentional essential tremor is more like cerebellar tremor than postural essential tremor. Brain Res. 2013;1529:188–99.PubMed CentralView ArticlePubMedGoogle Scholar
- Deuschl G, Raethjen J, Hellriegel H, Elble R. Treatment of patients with essential tremor. Lancet Neurol. 2011;2:148–61.View ArticleGoogle Scholar
- Elias WJ, Huss D, Voss T, Loomba J, Khaled M, Zadicario, et al. A pilot study of focused ultrasound thalamotomy for essential tremor. N Engl J Med. 2013;7:640–8.View ArticleGoogle Scholar
- Spiegel E, Wycis H, Szekely E, Adams D, Flanagan M, Baird H. Campotomy in various extrapyramidal disorders. J Neurosurg. 1963;20:871–84.View ArticlePubMedGoogle Scholar
- Bertrand C, Hardy J, Molina-Negro P, Martinez SN. Tremor of attitude. Confin Neurol. 1969;31:37–41.View ArticlePubMedGoogle Scholar
- Bertrand C, Hardy J, Molina-Negro P, Martinez SN. Optimum physiological target for arrest of tremor, Gillingham and Donaldson 3rd Symp. Parkinson’s disease, Livingstone, Edinburgh. 1969. p. 251–59.Google Scholar
- Ito Z. Stimulation and destruction of the prelemniscal radiation or its adjacent area in various extrapyramidal disorders. Confin Neurol. 1975;37:41–8.View ArticlePubMedGoogle Scholar
- Mundinger F, Riechert T. Stereotactic brain operations for the treatment of extrapyramidal movement disorders (parkinsonism and hyperkinesias) and their results. Fortschr Neurol Psychiatr. 1963;31:1–65. contd.PubMedGoogle Scholar
- Velasco FC, Molina-Negro P, Bertrand C, Hardy J. Further definition of the subthalamic target for arrest of tremor. J Neurosurg. 1972;36:184–91.View ArticlePubMedGoogle Scholar
- Jones EG. The thalamus, Cambridge University Press. 2nd ed. 2007.Google Scholar
- Morel A. Stereotactic atlas of the human thalamus and basal ganglia. New York: Informa Healthcare; 2007.View ArticleGoogle Scholar
- Morel A, Magnin M, Jeanmonod D. Multiarchitectonic and stereotactic atlas of the human thalamus. J Comp Neurol. 1997;387:588–630.View ArticlePubMedGoogle Scholar
- Hamani C, Dostrovsky JO, Lozano AM. The motor thalamus in neurosurgery. Neurosurgery. 2006;58:146–58.View ArticlePubMedGoogle Scholar
- Akbostanci MC, Slavin KV, Burchiel KJ. Stereotactic ventral intermedial thalamotomy for the treatment of essential tremor: results of a series of 37 patients. Stereotact Funct Neurosurg. 1999;72:174–7.View ArticlePubMedGoogle Scholar
- Cooper IS. A cerebellar mechanism in resting tremor. [In eng]. Neurology. 1966;16(10):1003–15.View ArticlePubMedGoogle Scholar
- Cooper IS. Cryogenic technique of thalamic surgery for parkinsonism and other involuntary movement disorders. Progr neurol Surg. 1973;5:159–88.View ArticleGoogle Scholar
- Cooper IS. Neurosurgical alleviation of intention tremor of multiple sclerosis and cerebellar disease. [In eng]. N Engl J Med. 1960;263:441–4.View ArticlePubMedGoogle Scholar
- Cooper IS. Neurosurgical relief of intention tremor due to cerebellar disease and multiple sclerosis. [In eng]. Arch Phys Med Rehabil. 1960;41:1–4.PubMedGoogle Scholar
- Goldman MS, Ahlskog JE, Kelly PJ. The symptomatic and functional outcome of stereotactic thalamotomy for medically intractable essential tremor. J Neurosurg. 1992;76(6):924–8.View ArticlePubMedGoogle Scholar
- Jankovic J, Cardoso F, Grossman RG, Hamilton WJ. Outcome after stereotactic thalamotomy for parkinsonian, essential, and other types of tremor. Neurosurgery. 1995;37(4):680–6. discussion 86-7.View ArticlePubMedGoogle Scholar
- Krayenbuhl H, Wyss OA, Yasargil MG. Bilateral thalamotomy and pallidotomy as treatment for bilateral parkinsonism. J Neurosurg. 1961;18:429–44.View ArticlePubMedGoogle Scholar
- Mohadjer M, Goerke H, Milios E, Etou A, Mundinger F. Long-term results of stereotaxy in the treatment of essential tremor. Stereotact Funct Neurosurg. 1990;54–55:125–9.View ArticlePubMedGoogle Scholar
- Zirh A, Reich SG, Dougherty PM, Lenz FA. Stereotactic thalamotomy in the treatment of essential tremor of the upper extremity: reassessment including a blinded measure of outcome. J Neurol Neurosurg Psychiatry. 1999;66(6):772–5.PubMed CentralView ArticlePubMedGoogle Scholar
- Blomstedt P, Hariz GM, Hariz MI, Koskinen LO. Thalamic deep brain stimulation in the treatment of essential tremor: a long-term follow-up. Br J Neurosurg. 2007;21(5):504–9.View ArticlePubMedGoogle Scholar
- Benabid AL, Pollak P, Gervason C, Hoffmann D, Gao DM, Hommel M, et al. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet. 1991;337(8738):403–6.View ArticlePubMedGoogle Scholar
- Benabid AL, Pollak P, Gao D, et al. Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as treatment of movement disorders. J Neurosurg. 1996;84:203–14.View ArticlePubMedGoogle Scholar
- Koller WC, Lyons KE, Wilkinson SB, Troster AI, Pahwa R. Long-term safety and efficacy of unilateral deep brain stimulation of the thalamus in essential tremor. Mov Disord. 2001;16(3):464–8.View ArticlePubMedGoogle Scholar
- Baizabal-Carvallo JF, Kagnoff MN, Jimenez-Shahed J, Fekete R, Jankovic J. The safety and efficacy of thalamic deep brain stimulation in essential tremor: 10 years and beyond. J Neurol Neurosurg Psychiatry. 2014;85(5):567–72.View ArticlePubMedGoogle Scholar
- Speelman JD, Schuurman R, De Bie RM, Esselink RA, Bosch DA. Stereotactic neurosurgery for tremor. Mov Disord. 2002;17 Suppl 3:S84–8.View ArticlePubMedGoogle Scholar
- Barbe MT, Liebhart L, Runge M, Deyng J, Florin E, Wojtecki L, et al. Deep brain stimulation of the ventral intermediate nucleus in patients with essential tremor: stimulation below intercommissural line is more efficient but equally effective as stimulation above. Exp Neurol. 2011;230(1):131–7.View ArticlePubMedGoogle Scholar
- Blomstedt P, Fytagoridis A, Tisch S. Deep brain stimulation of the posterior subthalamic area in the treatment of tremor. Acta Neurochir (Wien). 2009;151(1):31–6.View ArticleGoogle Scholar
- Blomstedt P, Sandvik U, Fytagoridis A, Tisch S. The posterior subthalamic area in the treatment of movement disorders: past, present, and future. Neurosurgery. 2009;64(6):1029–38. discussion 38-42.View ArticlePubMedGoogle Scholar
- Blomstedt P, Sandvik U, Hariz MI, Fytagoridis A, Forsgren L, Hariz GM, et al. Influence of age, gender and severity of tremor on outcome after thalamic and subthalamic DBS for essential tremor. Parkinsonism Relat Disord. 2011;17(8):617–20.View ArticlePubMedGoogle Scholar
- Fytagoridis A, Sandvik U, Astrom M, Bergenheim T, Blomstedt P. Long term follow-up of deep brain stimulation of the caudal zona incerta for essential tremor. J Neurol Neurosurg Psychiatry. 2012;83(3):258–62.View ArticlePubMedGoogle Scholar
- Hamel W, Herzog J, Kopper F, Pinsker M, Weinert D, Muller D, et al. Deep brain stimulation in the subthalamic area is more effective than nucleus ventralis intermedius stimulation for bilateral intention tremor. Acta Neurochir (Wien). 2007;149(8):749–58. discussion 58.View ArticleGoogle Scholar
- Jimenez F, Velasco F, Velasco M, Brito F, Morel C, Marquez I, et al. Subthalamic prelemniscal radiation stimulation for the treatment of Parkinson’s disease: electrophysiological characterization of the area. Arch Med Res. 2000;31(3):270–81.View ArticlePubMedGoogle Scholar
- Kitagawa M, Murata J, Kikuchi S, Sawamura Y, Saito H, Sasaki H, et al. Deep brain stimulation of subthalamic area for severe proximal tremor. Neurology. 2000;55:114–6.View ArticlePubMedGoogle Scholar
- Murata J, Kitagawa M, Uesugi H, Saito H, Iwasaki Y, Kikuchi S, et al. Electrical stimulation of the posterior subthalamic area for the treatment of intractable proximal tremor. J Neurosurg. 2003;99(4):708–15.View ArticlePubMedGoogle Scholar
- Plaha P, Javed S, Agombar D, O’ Farrell G, Khan S, Whone A, et al. Bilateral caudal zona incerta nucleus stimulation for essential tremor: outcome and quality of life. J Neurol Neurosurg Psychiatry. 2011;82(8):899–904.View ArticlePubMedGoogle Scholar
- Plaha P, Patel NK, Gill SS. Stimulation of the subthalamic region for essential tremor. J Neurosurg. 2004;101(1):48–54.View ArticlePubMedGoogle Scholar
- Sandvik U, Koskinen LO, Lundquist A, Blomstedt P. Thalamic and subthalamic deep brain stimulation for essential tremor: where is the optimal target? Neurosurgery. 2012;70(4):840–5. discussion 45-6.View ArticlePubMedGoogle Scholar
- Velasco F, Jimenez F, Perez ML, Carrillo-Ruiz JD, Velasco AL, Ceballos J, et al. Electrical stimulation of the prelemniscal radiation in the treatment of Parkinson’s disease: an old target revised with new techniques. Neurosurgery. 2001;49(2):293–306. discussion 06-8.PubMedGoogle Scholar
- Gallay MN, Jeanmonod D, Liu J, Morel A. Human pallidothalamic and cerebellothalamic tracts: anatomical basis for functional stereotactic neurosurgery. Brain Struct Funct. 2008;212(6):443–63.PubMed CentralView ArticlePubMedGoogle Scholar
- Condé F, Condé H. Demonstration of a rubrothalamic projection in the cat, with some comments on the origin of the rubrospinal tract. Neuroscience. 1980;54:789–802.View ArticleGoogle Scholar
- Hopkins DA, Lawrence DG. On the absence of a rubrothalamic projection in the monkey with observation on some ascending mesencephalic projections. J Comp Neurol. 1975;1612:269–93.View ArticleGoogle Scholar
- Louis ED. Linking essential tremor to the cerebellum: neuropathological evidence. cerebellum. 2015. [Epub ahead of print]Google Scholar
- Chang WS, Jung HH, Kweon EJ, Zadicario E, Rachmilevitch I, Chang JW. Unilateral magnetic resonance guided focused ultrasound thalamotomy for essential tremor: practices and clinicoradiological outcomes. J Neurol Neurosurg Psychiatry. 2015;86(3):257–64.View ArticlePubMedGoogle Scholar
- Jeanmonod D, Werner B, Morel A, Michels L, Zadicario E, Schiff G, et al. Transcranial magnetic resonance imaging-guided focused ultrasound: noninvasive central lateral thalamotomy for chronic neuropathic pain. Neurosurg Focus. 2012;32(1):E1.View ArticlePubMedGoogle Scholar
- Lipsman N, Schwartz ML, Huang Y, Lee L, Sankar T, Chapman M, et al. MR-guided focused ultrasound thalamotomy for essential tremor: a proof-of-concept study. Lancet Neurol. 2013;125:462–8.View ArticleGoogle Scholar
- Martin E, Jeanmonod D, Morel A, Zadicario E, Werner B. High-intensity focused ultrasound for noninvasive functional neurosurgery. Ann Neurol. 2009;66(6):858–61.View ArticlePubMedGoogle Scholar
- Magara A, Buhler R, Moser D, Kowalski M, Pourtehrani P, Jeanmonod D. First experience with MR-guided focused ultrasound in the treatment of Parkinson’s disease. J Ther Ultrasound. 2014;2:11.PubMed CentralView ArticlePubMedGoogle Scholar
- Moser D, Zadicario E, Schiff G, Jeanmonod D. Measurement of targeting accuracy in focused ultrasound functional neurosurgery. Neurosurg Focus. 2012;321:E2.View ArticleGoogle Scholar
- Moser D, Zadicario E, Schiff G, Jeanmonod D. MR-guided focused ultrasound technique in functional neurosurgery: targeting accuracy. J Ther Ultrasound. 2013;1:3.PubMed CentralView ArticlePubMedGoogle Scholar
- Magnin M, Jetzer U, Morel A, Jeanmonod D. Microelectrode recording and macrostimulation in thalamic and subthalamic MRI guided stereotactic surgery. Neurophysiol Clin. 2001;31:230–8.View ArticlePubMedGoogle Scholar
- Ledermann K, Jeanmonod D, McAleese S, Aufenberg C, Opwis K, Martin-Soelch C. Effects of cerebellothalamic tractotomy on cognitive and emotional functioning in essential tremor: a preliminary study in 5 essential tremor patients. Stereotactic Funct Neurosurg. 2015;932(19):127–32.View ArticleGoogle Scholar
- Fahn S, Tolosa E, Marin C. Clinical rating scale for tremor. In: Jankovic J, Tolosa E, editors. Parkinson’s disease and movement disorders. Munich: Urban and Schwarzenberg; 1993. p. 271–80.Google Scholar
- Nazzaro JM, Pahwa R, Lyons KE. Long-term benefits in quality of life after unilateral thalamic deep brain stimulation for essential tremor. J Neurosurg. 2012;117:156–61.View ArticlePubMedGoogle Scholar
- Schuurman PR, Bruins J, Merkus MP, Bosch DA, Speelman JD. A comparison of neuropsychological effects of thalamotomy and thalamic stimulation. Neurology. 2002;59(8):1232–9.View ArticlePubMedGoogle Scholar
- Schuurman PR, Bosch DA, Bossuyt PM, Bonsel GJ, van Someren EJ, De Bie RM, et al. A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor. N Engl J Med. 2000;342(7):461–8.View ArticlePubMedGoogle Scholar
- Vilkki J, Laitinen LV. Effects of pulvinotomy and ventrolateral thalamotomy on some cognitive functions. Neuropsychologia. 1976;14(1):67–78.View ArticlePubMedGoogle Scholar
- Bahgat D, Magill ST, Berk C, McCartney S, Burchiel KJ. Thalamotomy as a treatment option for tremor after ineffective deep brain stimulation. Stereotact Funct Neurosurg. 2013;91(1):18–23.View ArticlePubMedGoogle Scholar
- Bahgat D, Raslan AM, McCartney S, Burchiel KJ. Lesioning and stimulation in tremor-predominant movement disorder patients: an institutional case series and patient-reported outcome. Stereotact Funct Neurosurg. 2012;90(3):181–7.View ArticlePubMedGoogle Scholar
- Pahwa R, Lyons KE, Wilkinson SB, Simpson Jr RK, Ondo WG, Tarsy D, et al. Long-term evaluation of deep brain stimulation of the thalamus. J Neurosurg. 2006;104(4):506–12.View ArticlePubMedGoogle Scholar
- Borretzen MN, Bjerknes S, Saehle T, Skjelland M, Skogseid IM, Toft M, et al. Long-term follow-up of thalamic deep brain stimulation for essential tremor - patient satisfaction and mortality. BMC Neurol. 2014;14:120.PubMed CentralView ArticlePubMedGoogle Scholar
- Chopra A, Klassen BT, Stead M. Current clinical application of deep-brain stimulation for essential tremor. Neuropsychiatr Dis Treat. 2013;9:1859–65.PubMed CentralView ArticlePubMedGoogle Scholar
- Putzke JD, Uitti RJ, Obwegeser AA, Wszolek ZK, Wharen RE. Bilateral thalamic deep brain stimulation: midline tremor control. J Neurol Neurosurg Psychiatry. 2005;76(5):684–90.PubMed CentralView ArticlePubMedGoogle Scholar
- Hariz MI, Rehncrona S, Quinn NP, Speelman JD, Wensing C. Multicentre advanced Parkinson’s disease deep brain stimulation group. Multicenter study on deep brain stimulation in Parkinson’s disease: an independent assessment of reported adverse events at 4 years. Mov Disord. 2008;233:416–21.View ArticleGoogle Scholar
- Hooper AK, Okun MS, Foote KD, Fernandez HH, Jacobson C, Zeilman P, et al. Clinical cases where lesion therapy was chosen over deep brain stimulation. Stereotact Funct Neurosurg. 2008;86(3):147–52.View ArticlePubMedGoogle Scholar
- Martinez-Ramirez D, Morishita T, Zeilman PR, Peng-Chen Z, Foote KD, Okun MS. Atrophy and other potential factors affecting long term deep brain stimulation response: a case series. PLoS One. 2014;910:e111561.View ArticleGoogle Scholar
- Oh MY, Abosch A, Kim SH, Lang AE, Lozano AM. Long-term hardware-related complications of deep brain stimulation. Neurosurgery. 2002;50(6):1268–74. discussion 74-6.PubMedGoogle Scholar
- Semrau JA, Herter TM, Kiss ZH, Dukelow SP. Disruption in proprioception from long-term thalamic deep brain stimulation: a pilot study. Front Hum Neurosci. 2015;9:244.PubMed CentralView ArticlePubMedGoogle Scholar
- Zhang K, Bhatia S, Oh MY, Cohen D, Angle C, Whiting D. Long-term results of thalamic deep brain stimulation for essential tremor. J Neurosurg. 2010;112(6):1271–6.View ArticlePubMedGoogle Scholar
- Kondziolka D, Ong JG, Lee JY, Moore RY, Flickinger JC, Lunsford LD. Gamma knife thalamotomy for essential tremor. J Neurosurg. 2008;108(1):111–7.View ArticlePubMedGoogle Scholar
- Young RF, Li F, Vermeulen S, Meier R. Gamma knife thalamotomy for treatment of essential tremor: long-term results. J Neurosurg. 2010;112(6):1311–7.View ArticlePubMedGoogle Scholar