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Ricci A, Rubino E, Serra GP, Wallén-Mackenzie Å. Concerning neuromodulation as treatment of neurological and neuropsychiatric disorder: Insights gained from selective targeting of the subthalamic nucleus, para-subthalamic nucleus and zona incerta in rodents. Neuropharmacology 2024; 256:110003. [PMID: 38789078 DOI: 10.1016/j.neuropharm.2024.110003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 04/26/2024] [Accepted: 05/14/2024] [Indexed: 05/26/2024]
Abstract
Neuromodulation such as deep brain stimulation (DBS) is advancing as a clinical intervention in several neurological and neuropsychiatric disorders, including Parkinson's disease, dystonia, tremor, and obsessive-compulsive disorder (OCD) for which DBS is already applied to alleviate severely afflicted individuals of symptoms. Tourette syndrome and drug addiction are two additional disorders for which DBS is in trial or proposed as treatment. However, some major remaining obstacles prevent this intervention from reaching its full therapeutic potential. Side-effects have been reported, and not all DBS-treated individuals are relieved of their symptoms. One major target area for DBS electrodes is the subthalamic nucleus (STN) which plays important roles in motor, affective and associative functions, with impact on for example movement, motivation, impulsivity, compulsivity, as well as both reward and aversion. The multifunctionality of the STN is complex. Decoding the anatomical-functional organization of the STN could enhance strategic targeting in human patients. The STN is located in close proximity to zona incerta (ZI) and the para-subthalamic nucleus (pSTN). Together, the STN, pSTN and ZI form a highly heterogeneous and clinically important brain area. Rodent-based experimental studies, including opto- and chemogenetics as well as viral-genetic tract tracings, provide unique insight into complex neuronal circuitries and their impact on behavior with high spatial and temporal precision. This research field has advanced tremendously over the past few years. Here, we provide an inclusive review of current literature in the pre-clinical research fields centered around STN, pSTN and ZI in laboratory mice and rats; the three highly heterogeneous and enigmatic structures brought together in the context of relevance for treatment strategies. Specific emphasis is placed on methods of manipulation and behavioral impact.
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Affiliation(s)
- Alessia Ricci
- Uppsala University, Department of Organism Biology, 756 32 Uppsala, Sweden; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA
| | - Eleonora Rubino
- Uppsala University, Department of Organism Biology, 756 32 Uppsala, Sweden; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA
| | - Gian Pietro Serra
- Uppsala University, Department of Organism Biology, 756 32 Uppsala, Sweden; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA
| | - Åsa Wallén-Mackenzie
- Uppsala University, Department of Organism Biology, 756 32 Uppsala, Sweden; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.
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Neudorfer C, Kultas-Ilinsky K, Ilinsky I, Paschen S, Helmers AK, Cosgrove GR, Richardson RM, Horn A, Deuschl G. The role of the motor thalamus in deep brain stimulation for essential tremor. Neurotherapeutics 2024; 21:e00313. [PMID: 38195310 PMCID: PMC11103222 DOI: 10.1016/j.neurot.2023.e00313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 12/10/2023] [Accepted: 12/27/2023] [Indexed: 01/11/2024] Open
Abstract
The advent of next-generation technology has significantly advanced the implementation and delivery of Deep Brain Stimulation (DBS) for Essential Tremor (ET), yet controversies persist regarding optimal targets and networks responsible for tremor genesis and suppression. This review consolidates key insights from anatomy, neurology, electrophysiology, and radiology to summarize the current state-of-the-art in DBS for ET. We explore the role of the thalamus in motor function and describe how differences in parcellations and nomenclature have shaped our understanding of the neuroanatomical substrates associated with optimal outcomes. Subsequently, we discuss how seminal studies have propagated the ventral intermediate nucleus (Vim)-centric view of DBS effects and shaped the ongoing debate over thalamic DBS versus stimulation in the posterior subthalamic area (PSA) in ET. We then describe probabilistic- and network-mapping studies instrumental in identifying the local and network substrates subserving tremor control, which suggest that the PSA is the optimal DBS target for tremor suppression in ET. Taken together, DBS offers promising outcomes for ET, with the PSA emerging as a better target for suppression of tremor symptoms. While advanced imaging techniques have substantially improved the identification of anatomical targets within this region, uncertainties persist regarding the distinct anatomical substrates involved in optimal tremor control. Inconsistent subdivisions and nomenclature of motor areas and other subdivisions in the thalamus further obfuscate the interpretation of stimulation results. While loss of benefit and habituation to DBS remain challenging in some patients, refined DBS techniques and closed-loop paradigms may eventually overcome these limitations.
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Affiliation(s)
- Clemens Neudorfer
- Brain Modulation Lab, Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, 02114, USA; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Brain Circuit Therapeutics Department of Neurology Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA; Movement Disorder and Neuromodulation Unit, Department of Neurology, Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
| | | | - Igor Ilinsky
- Department of Anatomy and Cell Biology, The University of Iowa, Iowa City, IA, USA
| | - Steffen Paschen
- Department of Neurology, Christian-Albrechts-University, Kiel, Germany
| | | | - G Rees Cosgrove
- Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
| | - R Mark Richardson
- Brain Modulation Lab, Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, 02114, USA; Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Andreas Horn
- Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Center for Brain Circuit Therapeutics Department of Neurology Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA; Movement Disorder and Neuromodulation Unit, Department of Neurology, Charité -Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Günther Deuschl
- Department of Neurology, Christian-Albrechts-University, Kiel, Germany
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Chandra V, Hilliard JD, Foote KD. Deep brain stimulation for the treatment of tremor. J Neurol Sci 2022; 435:120190. [DOI: 10.1016/j.jns.2022.120190] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2021] [Revised: 02/07/2022] [Accepted: 02/17/2022] [Indexed: 01/15/2023]
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Nowacki A, Barlatey S, Al-Fatly B, Dembek T, Bot M, Green AL, Kübler D, Lachenmayer ML, Debove I, Segura-Amil A, Horn A, Visser-Vandewalle V, Schuurman R, Barbe M, Aziz TZ, Kühn AA, Nguyen TAK, Pollo C. Probabilistic mapping reveals optimal stimulation site in essential tremor. Ann Neurol 2022; 91:602-612. [PMID: 35150172 DOI: 10.1002/ana.26324] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 01/07/2022] [Accepted: 02/07/2022] [Indexed: 11/05/2022]
Abstract
OBJECTIVE To obtain individual clinical and neuroimaging data of patients undergoing Deep Brain Stimulation for essential tremor from five different European centers to identify predictors of outcome and to identify an optimal stimulation site. METHODS We analysed retrospectively baseline covariates, pre- and postoperative clinical tremor scores (12-month) as well as individual imaging data from 119 patients to obtain individual electrode positions and stimulation volumes. Individual imaging and clinical data was used to calculate a probabilistic stimulation map in normalized space using voxel-wise statistical analysis. Finally, we used this map to train a classifier to predict tremor improvement. RESULTS Probabilistic mapping of stimulation effects yielded a statistically significant cluster that was associated with a tremor improvement greater than 50%. This cluster of optimal stimulation extended from the posterior subthalamic area to the ventralis intermedius nucleus and coincided with a normative structural-connectivity-based cerebello-thalamic tract (CTT). The combined features "distance between the stimulation volume and the significant cluster" and "CTT activation" were used as a predictor of tremor improvement. This correctly classified a greater than 50% tremor improvement with a sensitivity of 89% and a specificity of 57%. INTERPRETATION Our multicentre ET probabilistic stimulation map identified an area of optimal stimulation along the course of the CTT. The results of this study are mainly descriptive until confirmed in independent datasets, ideally through prospective testing. This target will be made openly available and may be used to guide surgical planning and for computer-assisted programming of deep brain stimulation in the future. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Andreas Nowacki
- Department of Neurosurgery, Inselspital, Bern University Hospital, University Bern, Bern, Switzerland
| | - Sabry Barlatey
- Department of Neurosurgery, Inselspital, Bern University Hospital, University Bern, Bern, Switzerland
| | - Bassam Al-Fatly
- Charite-Universitätsmedizin Berlin, Movement Disorders and Neuromodulation Unit, Department of Neurology, Germany
| | - Till Dembek
- Department of Neurology, University Hospital Cologne, Cologne, Germany
| | - Maarten Bot
- Department of Neurosurgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Alexander L Green
- Nuffield Department of Clinical Neuroscience and Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United King
| | - Dorothee Kübler
- Charite-Universitätsmedizin Berlin, Movement Disorders and Neuromodulation Unit, Department of Neurology, Germany
| | - M Lenard Lachenmayer
- Department of Neurology, Inselspital, Bern University Hospital, University Bern, Bern, Switzerland
| | - Ines Debove
- Department of Neurology, Inselspital, Bern University Hospital, University Bern, Bern, Switzerland
| | - Alba Segura-Amil
- Department of Neurosurgery, Inselspital, Bern University Hospital, University Bern, Bern, Switzerland.,ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland
| | - Andreas Horn
- Charite-Universitätsmedizin Berlin, Movement Disorders and Neuromodulation Unit, Department of Neurology, Germany
| | - Veerle Visser-Vandewalle
- Department of Stereotactic and Functional Neurosurgery, University Hospital Cologne, and University of Cologne, Faculty of Medicine, Cologne, Germany
| | - Rick Schuurman
- Department of Neurosurgery, Academic Medical Center, Amsterdam, The Netherlands
| | - Michael Barbe
- Department of Neurology, University Hospital Cologne, Cologne, Germany
| | - Tipu Z Aziz
- Nuffield Department of Clinical Neuroscience and Nuffield Department of Surgical Sciences, University of Oxford, Oxford, United King
| | - Andrea A Kühn
- Charite-Universitätsmedizin Berlin, Movement Disorders and Neuromodulation Unit, Department of Neurology, Germany
| | - T A Khoa Nguyen
- Department of Neurosurgery, Inselspital, Bern University Hospital, University Bern, Bern, Switzerland.,ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland
| | - Claudio Pollo
- Department of Neurosurgery, Inselspital, Bern University Hospital, University Bern, Bern, Switzerland
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Park G, Shin W, Park Y, Chung S, Kim D, Kim J. Neural correlates of multidimensional motor outputs in an excitatory parafascicular-zona incerta circuit. Biochem Biophys Res Commun 2022; 591:102-109. [PMID: 35007833 DOI: 10.1016/j.bbrc.2021.12.036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 12/13/2021] [Indexed: 11/21/2022]
Abstract
The parafascicular nucleus (Pf) in medial thalamus is interconnected with prefrontal cortex and basal ganglia. Though much research has determined its importance in cognitive regulation of behaviour, its projections to regions in subthalamus remain less known. Such connections include those to zona incerta (ZI), located immediately dorsal to subthalamic nuclei (STN) regulating motor output, and whose role in a motor context is only beginning to be investigated. We thus examined circuits from parafascicular (Pf) thalamus to ZI, and its activity during locomotion and spontaneous behaviours in mice. We found that a distinct group of CaMKIIα-positive excitatory parafascicular neurons, separated from VGLUT2-positive excitatory neurons, project widely into ZI, more than adjacent STN. Our results from fibre photometry and decoding with general linear model (GLM) indicate that PF-ZI pathways do not specifically correlate with amount of locomotion or movement velocity, but instead show more specified activity during relative directional changes of movements observed in turning, sniffing behaviours. These results hint at the PF-ZI pathway having a distinct role in directing action specificity and have implications for subcortical bases in dimensional control of behaviours.
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Affiliation(s)
- Geunhong Park
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea; Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea
| | - Wooyeon Shin
- Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea; Program of Brain and Cognitive Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea
| | - Yongjun Park
- Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea; Division of Bio-Medical Science & Technology, University of Science and Technology (UST), Daejeon, South Korea
| | - Sooyoung Chung
- Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea
| | - Daesoo Kim
- Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, South Korea.
| | - Jeongjin Kim
- Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul, South Korea; Division of Bio-Medical Science & Technology, University of Science and Technology (UST), Daejeon, South Korea.
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Riskin-Jones HH, Kashanian A, Sparks H, Tsolaki E, Pouratian N. Increased structural connectivity of thalamic stimulation sites to motor cortex relates to tremor suppression. NEUROIMAGE-CLINICAL 2021; 30:102628. [PMID: 33773164 PMCID: PMC8024765 DOI: 10.1016/j.nicl.2021.102628] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 02/17/2021] [Accepted: 03/07/2021] [Indexed: 11/28/2022]
Abstract
Clinically weighted tractography reveals key patterns of therapeutic brain stimulation. Thalamic stimulation for tremor preferentially connects to precentral gyrus and cerebellum. Thalamic DBS of areas most connected to motor cortex results in superior outcomes. Acute and chronic therapeutic outcomes demonstrate converging connectivity patterns. Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM-DBS) is a highly successful treatment for medication-refractory essential tremor (ET). Clinical outcomes are dependent on accurate targeting. Here, we aim to develop a framework for connectivity-guided DBS targeting by evaluating probabilistic tractography and clinical response at both initial programming (IP) and clinical follow-up (CF). Magnetic resonance imaging and clinical outcomes were evaluated in 23 ET patients who were treated by VIM-DBS at the University of California Los Angeles (20 at IP, 18 at CF, 14 at both). Lead-DBS was used to model the volume of tissue activated tissue (VTA) based on programming configurations at both IP and CF. Probabilistic tractography, calculated in FSL, was used to evaluate 1) clinically weighted whole brain connectivity of VTA; 2) connectivity between VTA and freesurfer-derived target regions of interest (ROI) including primary motor, premotor, and prefrontal cortices, and cerebellum; and 3) volume of intersection between VTA and probabilistic tractography-based segmentation of the thalamus. At IP, individual contacts were scored as high or low efficacy based on acute tremor improvement. At CF, clinical response was measured by percent of change of the Clinical Rating Scale for Tremor (CRST) compared to preoperative scores. Contributions from each target ROI to clinical response was measured using logistic regression for IP and linear regression for CF. The clinically weighted map of whole brain connectivity of VTA shows preferential connectivity to precentral gyrus and brainstem/cerebellum. The volume of intersection between VTA and thalamic segmentation map based on probabilistic connectivity to primary motor cortex was a significant predictor of contact efficacy at IP (OR = 2.26 per 100 mm3 of overlap, p = .04) and percent change in CRST at CF (β = 14.67 per 100 mm3 of overlap, p = .003). Targeting DBS to the area of thalamus most connected to primary motor cortex based on probabilistic tractography is associated with superior outcomes, providing a potential guide not only for lead targeting but also therapeutic programming.
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Affiliation(s)
- Hannah H Riskin-Jones
- Department of Neurosurgery, 300 UCLA Stein Plaza, Suite 562, David Geffen School of Medicine at UCLA (University of California, Los Angeles), Los Angeles, CA, United States
| | - Alon Kashanian
- Department of Neurosurgery, 300 UCLA Stein Plaza, Suite 562, David Geffen School of Medicine at UCLA (University of California, Los Angeles), Los Angeles, CA, United States
| | - Hiro Sparks
- Department of Neurosurgery, 300 UCLA Stein Plaza, Suite 562, David Geffen School of Medicine at UCLA (University of California, Los Angeles), Los Angeles, CA, United States
| | - Evangelia Tsolaki
- Department of Neurosurgery, 300 UCLA Stein Plaza, Suite 562, David Geffen School of Medicine at UCLA (University of California, Los Angeles), Los Angeles, CA, United States
| | - Nader Pouratian
- Department of Neurosurgery, 300 UCLA Stein Plaza, Suite 562, David Geffen School of Medicine at UCLA (University of California, Los Angeles), Los Angeles, CA, United States.
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Philipson J, Blomstedt P, Hariz M, Jahanshahi M. Deep brain stimulation in the caudal zona incerta in patients with essential tremor: effects on cognition 1 year after surgery. J Neurosurg 2021; 134:208-215. [PMID: 31860827 DOI: 10.3171/2019.9.jns191646] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 09/23/2019] [Indexed: 11/06/2022]
Abstract
OBJECTIVE The ventral intermediate nucleus (VIM) of the thalamus is currently the established target in the use of deep brain stimulation (DBS) to treat essential tremor (ET). In recent years, the caudal zona incerta (cZi), a brain target commonly used during the lesional era, has been revived as the primary target in a number of DBS studies that show evidence of the efficacy of cZi targeting in DBS treatment for controlling the symptoms of ET. The authors sought to obtain comprehensive neuropsychological data and thoroughly investigate the cognitive effects of cZi targeting in patients with ET treated with DBS. METHODS Twenty-six consecutive patients with ET who received DBS with cZi as the target at our department from December 2012 to February 2017 were included in this study. All patients were assessed using a comprehensive neuropsychological test battery covering the major cognitive domains both preoperatively and 12 months postoperatively. RESULTS The results show no major adverse effects on patient performance on the tests of cognitive function other than a slight decline of semantic verbal fluency. CONCLUSIONS This study indicates that the cZi is a safe target from a cognitive perspective in the treatment of ET with DBS.
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Affiliation(s)
- Johanna Philipson
- 1Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden
| | - Patric Blomstedt
- 1Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden
| | - Marwan Hariz
- 1Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden
- 2Unit of Functional Neurosurgery, UCL Institute of Neurology, London, United Kingdom; and
| | - Marjan Jahanshahi
- 2Unit of Functional Neurosurgery, UCL Institute of Neurology, London, United Kingdom; and
- 3The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China
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Iorio-Morin C, Fomenko A, Kalia SK. Deep-Brain Stimulation for Essential Tremor and Other Tremor Syndromes: A Narrative Review of Current Targets and Clinical Outcomes. Brain Sci 2020; 10:E925. [PMID: 33271848 PMCID: PMC7761254 DOI: 10.3390/brainsci10120925] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 11/25/2020] [Accepted: 11/30/2020] [Indexed: 02/06/2023] Open
Abstract
Tremor is a prevalent symptom associated with multiple conditions, including essential tremor (ET), Parkinson's disease (PD), multiple sclerosis (MS), stroke and trauma. The surgical management of tremor evolved from stereotactic lesions to deep-brain stimulation (DBS), which allowed safe and reversible interference with specific neural networks. This paper reviews the current literature on DBS for tremor, starting with a detailed discussion of current tremor targets (ventral intermediate nucleus of the thalamus (Vim), prelemniscal radiations (Raprl), caudal zona incerta (Zi), thalamus (Vo) and subthalamic nucleus (STN)) and continuing with a discussion of results obtained when performing DBS in the various aforementioned tremor syndromes. Future directions for DBS research are then briefly discussed.
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Affiliation(s)
- Christian Iorio-Morin
- Christian Iorio-Morin, Division of Neurosurgery, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC J1H 5N4, Canada
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON M5T 2S8, Canada; (A.F.); (S.K.K.)
| | - Anton Fomenko
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON M5T 2S8, Canada; (A.F.); (S.K.K.)
| | - Suneil K. Kalia
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, ON M5T 2S8, Canada; (A.F.); (S.K.K.)
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Structure-function relationship of the posterior subthalamic area with directional deep brain stimulation for essential tremor. NEUROIMAGE-CLINICAL 2020; 28:102486. [PMID: 33395977 PMCID: PMC7674616 DOI: 10.1016/j.nicl.2020.102486] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 10/10/2020] [Accepted: 10/25/2020] [Indexed: 11/21/2022]
Abstract
Directional DBS of the DRTT and the zona incerta is correlated with tremor suppression. Activation patterns for tremor suppression and side effects involve mostly the dentato-rubro-thalamic tract and the zona incerta. Concomitant side effects often limit the therapeutic window of directional deep brain stimulation. Deep Brain Stimulation of the posterior subthalamic area is an emergent target for the treatment of Essential Tremor. Due to the heterogeneous and complex anatomy of the posterior subthalamic area, it remains unclear which specific structures mediate tremor suppression and different side effects. The objective of the current work was to yield a better understanding of what anatomical structures mediate the different clinical effects observed during directional deep brain stimulation of that area. We analysed a consecutive series of 12 essential tremor patients. Imaging analysis and systematic clinical testing performed 4–6 months postoperatively yielded location, clinical efficacy and corresponding therapeutic windows for 160 directional contacts. Overlap ratios between individual activation volumes and neighbouring thalamic and subthalamic nuclei as well as individual fiber tracts were calculated. Further, we generated stimulation heatmaps to assess the area of activity and structures stimulated during tremor suppression and occurrence of side effects. Stimulation of the dentato-rubro-thalamic tract and the zona incerta was most consistently correlated with tremor suppression. Both individual and group analysis demonstrated a similar pattern of activation for tremor suppression and different sorts of side-effects. Unlike current clinical concepts, induction of spasms and paresthesia were not correlated with stimulation of the corticospinal tract and the medial lemniscus. Furthermore, we noticed a significant difference in the therapeutic window between the best and worst directional contacts. The best directional contacts did not provide significantly larger therapeutic windows than omnidirectional stimulation at the same level. Deep brain stimulation of the posterior subthalamic area effectively suppresses all aspects of ET but can be associated with concomitant side effects limiting the therapeutic window. Activation patterns for tremor suppression and side effects were similar and predominantly involved the dentato-rubro-thalamic tract and the zona incerta. We found no different activation patterns between different types of side effects and no clear correlation between structure and function. Future studies with use of more sophisticated modelling of activation volumes taking into account fiber heterogeneity and orientation may eventually better delineate these different clusters, which may allow for a refined targeting and programming within this area.
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10
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Abstract
Essential tremor is one of the most common tremor syndromes. According to the recent tremor classification, tremor as a symptom is defined as an involuntary, rhythmic, oscillatory movement of a body part and is classified along two axes: axis 1-defining syndromes based on the clinical features such as historical features, tremor characteristics, associated signs, and laboratory tests; and axis 2-classifying the etiology (Bhatia et al., Mov Disord 33:75-87, 2018). The management of this condition has two major approaches. The first is to exclude treatable etiologies, as particularly during the onset of this condition the presentation of a variety of etiologies can be with monosymptomatic tremor. Once the few etiologies with causal treatments are excluded, all further treatment is symptomatic. Shared decision-making with enabling the patient to knowledgeably choose treatment options is needed to customize the management. Mild to moderate tremor severity can sometimes be controlled with occupational treatment, speech therapy of psychotherapy, or adaptation of coping strategy. First-line pharmacological treatments include symptomatic treatment with propranolol, primidone, and topiramate. Botulinum toxin is for selected cases. Invasive treatments for essential tremor should be considered for severe tremors. They are generally accepted as the most powerful interventions and provide not only improvement of tremor but also a significant improvement of life quality. The current standard is deep brain stimulation (DBS) of the thalamic and subthalamic region. Focused ultrasound thalamotomy is a new therapy attracting increasing interest. Radiofrequency lesioning is only rarely done if DBS or focused ultrasound is not possible. Radiosurgery is not well established. We present our treatment algorithm.
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Affiliation(s)
- Franziska Hopfner
- Department of Neurology, UKSH, Christian-Albrechts-University Kiel, Rosalind-Fraenklinstr. 10, 24105, Kiel, Germany
- Department of Neurology, Hannover Medical School, Hannover, Germany
| | - Günther Deuschl
- Department of Neurology, UKSH, Christian-Albrechts-University Kiel, Rosalind-Fraenklinstr. 10, 24105, Kiel, Germany.
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Breysse E, Meffre J, Pelloux Y, Winstanley CA, Baunez C. Decreased risk‐taking and loss‐chasing after subthalamic nucleus lesion in rats. Eur J Neurosci 2020; 53:2362-2375. [DOI: 10.1111/ejn.14895] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 06/27/2020] [Accepted: 06/29/2020] [Indexed: 12/20/2022]
Affiliation(s)
- Emmanuel Breysse
- Institut de Neurosciences de la Timone UMR7289 CNRS & Aix‐Marseille Université Marseille France
| | - Julie Meffre
- Institut de Neurosciences de la Timone UMR7289 CNRS & Aix‐Marseille Université Marseille France
- Laboratoire de Neurosciences Cognitives UMR7289 CNRS & Aix‐Marseille Université Marseille France
| | - Yann Pelloux
- Institut de Neurosciences de la Timone UMR7289 CNRS & Aix‐Marseille Université Marseille France
- IIT Genoa Italy
| | - Catharine A. Winstanley
- Department of Psychology Djavad Mowafaghian Centre for Brain HealthUniversity of British Columbia Vancouver BC Canada
| | - Christelle Baunez
- Institut de Neurosciences de la Timone UMR7289 CNRS & Aix‐Marseille Université Marseille France
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12
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Zsigmond P, Wårdell K. Optical Measurements during Asleep Deep Brain Stimulation Surgery along Vim-Zi Trajectories. Stereotact Funct Neurosurg 2020; 98:55-61. [PMID: 32079023 DOI: 10.1159/000505708] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 12/31/2019] [Indexed: 11/19/2022]
Abstract
BACKGROUND Optics can be used for guidance in deep brain stimulation (DBS) surgery. The aim was to use laser Doppler flowmetry (LDF) to investigate the intraoperative optical trajectory along the ventral intermediate nucleus (VIM) and zona incerta (Zi) regions in patients with essential tremor during asleep DBS surgery, and whether the Zi region could be identified. METHODS A forward-looking LDF guide was used for creation of the trajectory for the DBS lead, and the microcirculation and tissue greyness, i.e., total light intensity (TLI) was measured along 13 trajectories. TLI trajectories and the number of high-perfusion spots were investigated at 0.5-mm resolution in the last 25 mm from the targets. RESULTS All implantations were done without complications and with significant improvement of tremor (p < 0.01). Out of 798 measurements, 12 tissue spots showed high blood flow. The blood flow was significantly higher in VIM than in Zi (p < 0.001). The normalized mean TLI curve showed a significant (p < 0.001) lower TLI in the VIM region than in the Zi region. CONCLUSION Zi DBS performed asleep appears to be safe and effective. LDF monitoring provides direct in vivomeasurement of the microvascular blood flow in front of the probe, which can help reduce the risk of hemorrhage. LDF can differentiate between the grey substance in the thalamus and the transmission border entering the posterior subthalamic area where the tissue consists of more white matter tracts.
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Affiliation(s)
- Peter Zsigmond
- Departments of Neurosurgery and Clinical and Experimental Medicine, Linköping University, Linköping, Sweden,
| | - Karin Wårdell
- Department of Biomedical Engineering, Linköping University, Linköping, Sweden
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O’Shea SA, Elkind M, Pullman SL, Ford B. Holmes Tremor due to Artery of Percheron Infarct: Clinical Case and Treatment Using Deep Brain Stimulation of the Vim and ZI Targets. Tremor Other Hyperkinet Mov (N Y) 2020; 10:tre-10-732. [PMID: 32195040 PMCID: PMC7070701 DOI: 10.7916/tohm.v0.732] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Accepted: 12/05/2019] [Indexed: 04/12/2023] Open
Abstract
BACKGROUND Holmes tremor (HT) arises from disruption of the cerebellothalamocortical pathways. A lesion can interrupt the projection at any point, resulting in this tremor. We describe a case of HT due to the rare artery of Percheron infarct and its successful treatment using deep brain stimulation. CASE REPORT A 62-year-old woman with a right medial cerebral peduncle and bilateral thalamic stroke developed HT. Ventral intermediate nucleus (Vim) zona incerta (ZI) deep brain stimulation (DBS) surgery was performed, with improvement in her tremor. DISCUSSION Our case supports the theory that the more caudal ZI target in combination with Vim is beneficial in treating poorly DBS-responsive tremors such as HT.
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Affiliation(s)
- Sarah A. O’Shea
- Department of Neurology, Boston University School of Medicine, Boston University, Boston, MA, USA
- Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
- To whom correspondence should be addressed. E-mail:
| | - Mitchell Elkind
- Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
- Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Seth L. Pullman
- Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
| | - Blair Ford
- Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
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14
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Bot M, van Rootselaar F, Contarino MF, Odekerken V, Dijk J, de Bie R, Schuurman R, van den Munckhof P. Deep Brain Stimulation for Essential Tremor: Aligning Thalamic and Posterior Subthalamic Targets in 1 Surgical Trajectory. Oper Neurosurg (Hagerstown) 2019; 15:144-152. [PMID: 29281074 DOI: 10.1093/ons/opx232] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2017] [Accepted: 10/04/2017] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Ventral intermediate nucleus (VIM) deep brain stimulation (DBS) and posterior subthalamic area (PSA) DBS suppress tremor in essential tremor (ET) patients, but it is not clear which target is optimal. Aligning both targets in 1 surgical trajectory would facilitate exploring stimulation of either target in a single patient. OBJECTIVE To evaluate aligning VIM and PSA in 1 surgical trajectory for DBS in ET. METHODS Technical aspects of trajectories, intraoperative stimulation findings, final electrode placement, target used for chronic stimulation, and adverse and beneficial effects were evaluated. RESULTS In 17 patients representing 33 trajectories, we successfully aligned VIM and PSA targets in 26 trajectories. Trajectory distance between targets averaged 7.2 (range 6-10) mm. In all but 4 aligned trajectories, optimal intraoperative tremor suppression was obtained in the PSA. During follow-up, active electrode contacts were located in PSA in the majority of cases. Overall, successful tremor control was achieved in 69% of patients. Stimulation-induced dysarthria or gait ataxia occurred in, respectively, 56% and 44% of patients. Neither difference in tremor suppression or side effects was noted between aligned and nonaligned leads nor between the different locations of chronic stimulation. CONCLUSION Alignment of VIM and PSA for DBS in ET is feasible and enables intraoperative exploration of both targets in 1 trajectory. This facilitates positioning of electrode contacts in both areas, where multiple effective points of stimulation can be found. In the majority of aligned leads, optimal intraoperative and chronic stimulation were located in the PSA.
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Affiliation(s)
- Maarten Bot
- Department of Neurosurgery, Academic Medical Center, Amsterdam, The Nether-lands
| | - Fleur van Rootselaar
- Department of Neurology and Clinical Neurophysiology, Academic Med-ical Center, Amsterdam, The Netherlands
| | - Maria Fiorella Contarino
- Department of Neurology, Haga Teach-ing Hospital, The Hague, The Netherlands.,Department of Neurology, Leiden Uni-versity Medical Center, Leiden, The Netherlands
| | - Vincent Odekerken
- Department of Neurology and Clinical Neurophysiology, Academic Med-ical Center, Amsterdam, The Netherlands
| | - Joke Dijk
- Department of Neurology and Clinical Neurophysiology, Academic Med-ical Center, Amsterdam, The Netherlands
| | - Rob de Bie
- Department of Neurology and Clinical Neurophysiology, Academic Med-ical Center, Amsterdam, The Netherlands
| | - Richard Schuurman
- Department of Neurosurgery, Academic Medical Center, Amsterdam, The Nether-lands
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15
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Nordin T, Zsigmond P, Pujol S, Westin CF, Wårdell K. White matter tracing combined with electric field simulation - A patient-specific approach for deep brain stimulation. Neuroimage Clin 2019; 24:102026. [PMID: 31795055 PMCID: PMC6880013 DOI: 10.1016/j.nicl.2019.102026] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Revised: 09/04/2019] [Accepted: 10/02/2019] [Indexed: 11/23/2022]
Abstract
OBJECTIVE Deep brain stimulation (DBS) in zona incerta (Zi) is used for symptom alleviation in essential tremor (ET). Zi is positioned along the dentato-rubro-thalamic tract (DRT). Electric field simulations with the finite element method (FEM) can be used for estimation of a volume where the stimulation affects the tissue by applying a fixed isolevel (VDBS). This work aims to develop a workflow for combined patient-specific electric field simulation and white matter tracing of the DRT, and to investigate the influence on the VDBS from different brain tissue models, lead design and stimulation modes. The novelty of this work lies in the combination of all these components. METHOD Patients with ET were implanted in Zi (lead 3389, n = 3, voltage mode; directional lead 6172, n = 1, current mode). Probabilistic reconstruction from diffusion MRI (dMRI) of the DRT (n = 8) was computed with FSL Toolbox. Brain tissue models were created for each patient (two homogenous, one heterogenous isotropic, one heterogenous anisotropic) and the respective VDBS (n = 48) calculated from the Comsol Multiphysics FEM simulations. The DRT and VDBS were visualized with 3DSlicer and superimposed on the preoperative T2 MRI, and the common volumes calculated. Dice Coefficient (DC) and level of anisotropy were used to evaluate and compare the brain models. RESULT Combined patient-specific tractography and electric field simulation was designed and evaluated, and all patients showed benefit from DBS. All VDBS overlapped the reconstructed DRT. Current stimulation showed prominent difference between the tissue models, where the homogenous grey matter deviated most (67 < DC < 69). Result from heterogenous isotropic and anisotropic models were similar (DC > 0.95), however the anisotropic model consistently generated larger volumes related to a greater extension of the electric field along the DBS lead. Independent of tissue model, the steering effect of the directional lead was evident and consistent. CONCLUSION A workflow for patient-specific electric field simulations in combination with reconstruction of DRT was successfully implemented. Accurate tissue classification is essential for electric field simulations, especially when using the current control stimulation. With an accurate targeting and tractography reconstruction, directional leads have the potential to tailor the electric field into the desired region.
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Affiliation(s)
- Teresa Nordin
- Department of Biomedical Engineering, Linköping University, Sweden.
| | - Peter Zsigmond
- Department of Neurosurgery and Clinical and Experimental Medicine, Linköping University, Sweden
| | - Sonia Pujol
- Laboratory of Mathematics in Imaging, Brigham and Women's Hospital, Harvard Medical School, USA; Surgical Planning Laboratory, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, USA
| | - Carl-Fredrik Westin
- Laboratory of Mathematics in Imaging, Brigham and Women's Hospital, Harvard Medical School, USA
| | - Karin Wårdell
- Department of Biomedical Engineering, Linköping University, Sweden
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Fernandez-Garcia C, Alonso-Frech F, Monje MHG, Matias-Guiu J. Role of deep brain stimulation therapy in the magnetic resonance-guided high-frequency focused ultrasound era: current situation and future prospects. Expert Rev Neurother 2019; 20:7-21. [PMID: 31623494 DOI: 10.1080/14737175.2020.1677465] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Introduction: Deep brain stimulation (DBS) is a well-established treatment of movement disorders; but recently there has been an increasing trend toward the ablative procedure magnetic resonance-guided focused ultrasound (MRgFU). DBS is an efficient neuromodulatory technique but associated with surgical complications. MRIgFUS is an incision-free method that allows thermal lesioning, with fewer surgical complications but irreversible effects.Areas covered: We look at current and prospective aspects of both techniques. In DBS, appropriate patient selection, improvement in surgical expertise, target accuracy (preoperative and intraoperative imaging), neurophysiological recordings, and novel segmented leads need to be considered. However, increased number of older patients with higher comorbidities and risk of DBS complications (mainly intracranial hemorrhage, but also infections, hardware complications) make them not eligible for surgery. With MRgFUS, hemorrhage risks are virtually nonexistent, infection or hardware malfunction are eliminated, while irreversible side effects can appear.Expert commentary: Comparison of the efficacy and risks associated with these techniques, in combination with a growing aged population in developed countries with higher comorbidities and a preference for less invasive treatments, necessitates a review of the indications for movement disorders and the most appropriate treatment modalities.
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Affiliation(s)
- C Fernandez-Garcia
- Department of Neurosurgery, Hospital Clínico San Carlos, San Carlos Research Health Institute (IdISSC), Madrid, Spain.,Medicine Department, Universidad Complutense, Madrid, Spain
| | - F Alonso-Frech
- Department of Neurology, Hospital Clínico San Carlos, San Carlos Research Health Institute (IdISSC), Universidad Complutense, Madrid, Spain.,HM CINAC, Hospital Universitario HM Puerta del Sur, Universidad CEU-San Pablo, Móstoles, Madrid, Spain
| | - M H G Monje
- HM CINAC, Hospital Universitario HM Puerta del Sur, Universidad CEU-San Pablo, Móstoles, Madrid, Spain
| | - J Matias-Guiu
- Medicine Department, Universidad Complutense, Madrid, Spain.,Department of Neurology, Hospital Clínico San Carlos, San Carlos Research Health Institute (IdISSC), Universidad Complutense, Madrid, Spain
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Ferreira JJ, Mestre TA, Lyons KE, Benito-León J, Tan EK, Abbruzzese G, Hallett M, Haubenberger D, Elble R, Deuschl G. MDS evidence-based review of treatments for essential tremor. Mov Disord 2019; 34:950-958. [PMID: 31046186 DOI: 10.1002/mds.27700] [Citation(s) in RCA: 108] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2018] [Revised: 03/25/2019] [Accepted: 03/27/2019] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Essential tremor is one of the most prevalent movement disorders. Many treatments for essential tremor have been reported in clinical practice, but it is uncertain which options have the most robust evidence. The International Parkinson and Movement Disorder Society commissioned a task force on tremor to review clinical studies of treatments for essential tremor. OBJECTIVES To conduct an evidence-based review of current pharmacological and surgical treatments for essential tremor, using standardized criteria defined a priori by the International Parkinson and Movement Disorder Society. METHODS We followed the recommendations of the International Parkinson and Movement Disorder Society Evidence Based Medicine Committee. RESULTS Sixty-four studies of pharmacological and surgical interventions were included in the review. Propranolol and primidone were classified as clinically useful, similar to Topiramate, but only for doses higher than 200 mg/day. Alprazolam and botulinum toxin type A were classified as possibly useful. Unilateral Ventralis intermedius thalamic DBS, radiofrequency thalamotomy, and MRI-guided focused ultrasound thalamotomy were considered possibly useful. All the above recommendations were made for limb tremor in essential tremor. There was insufficient evidence for voice and head tremor as well as for the remaining interventions. CONCLUSION Propranolol, primidone, and topiramate (>200 mg/day) are the pharmacological interventions in which the data reviewed robustly supported efficacy. Their safety profile and patient preference may guide the prioritization of these interventions in clinical practice. MRI-guided focused ultrasound thalamotomy was, for the first time, assessed and was considered to be possibly useful. There is a need to improve study design in essential tremor and overcome the limitation of small sample sizes, cross-over studies, short-term follow-up studies, and use of nonvalidated clinical scales. © 2019 International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Joaquim J Ferreira
- Instituto de Medicina Molecular, Faculty of Medicine, University of Lisbon, Portugal.,CNS-Campus Neurológico Sénior, Torres Vedras, Portugal
| | - Tiago A Mestre
- Parkinson's Disease and Movement Disorders Center, Division of Neurology, Department of Medicine, The Ottawa Hospital Research Institute, Brain and Mind Research Institute, University of Ottawa, Ottawa, Ontario, Canada
| | - Kelly E Lyons
- Parkinson's Disease and Movement Disorder Center, University of Kansas Medical Center, Kansas City, Kansas, USA
| | - Julián Benito-León
- Department of Neurology, University Hospital 12 de Octubre; Center of Biomedical Network Research on Neurodegenerative diseases (CIBERNED), Department of Medicine, Faculty of Medicine, Complutense University, Madrid, Spain
| | - Eng-King Tan
- National Neuroscience Institute, Duke NUS Medical School, Singapore
| | - Giovanni Abbruzzese
- Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, University of Genoa-IRCCS Ospedale Policlinico San Martino, Genova, Italy
| | - Mark Hallett
- Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
| | - Dietrich Haubenberger
- Clinical Trials Unit, Office of the Clinical Director, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
| | - Rodger Elble
- Department of Neurology, Southern Illinois University School of Medicine, Springfield, Illinois, USA
| | - Günther Deuschl
- Department of Neurology, Universitätsklinikum Schleswig-Holstein, Kiel Campus, Christian Albrechts University Kiel, Kiel, Germany
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Spears CC, Almeida L, Okun MS, Deeb W. An Unusual Case of Essential Tremor Deep Brain Stimulation: Where is the Lead? TREMOR AND OTHER HYPERKINETIC MOVEMENTS (NEW YORK, N.Y.) 2019; 9:617. [PMID: 30867977 PMCID: PMC6411417 DOI: 10.7916/d8-xj6w-cm53] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Accepted: 01/28/2019] [Indexed: 01/21/2023]
Abstract
Clinical Vignette A 73-year-old female with essential tremor (ET) underwent bilateral thalamic ventralis intermedius (Vim) deep brain stimulation (DBS) surgery. The leads provided tremor benefit, but the location was suboptimal and contributed to stimulation-induced hemichorea. Clinical Dilemma Can patients with ET derive benefit when stimulating outside the Vim? What do we know about stimulation-induced hemichorea in the setting of ET? Clinical Solution Lead localization combined with advanced programming strategies can be employed to troubleshoot DBS in settings when benefits are observed along with adverse effects. Gap in Knowledge Sparse information exists about DBS when applied to neuroanatomic regions outside the Vim for the management of ET. Subthalamic nucleus DBS-induced chorea has been reported in multiple movement disorders, but not in ET.
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Affiliation(s)
- C Chauncey Spears
- Department of Neurology, University of Michigan, Ann Arbor, MI, US.,Fixel Center for Neurological Diseases, Program in Movement Disorders and Neurorestoration, Department of Neurology, University of Florida, Gainesville, FL, US
| | - Leonardo Almeida
- Fixel Center for Neurological Diseases, Program in Movement Disorders and Neurorestoration, Department of Neurology, University of Florida, Gainesville, FL, US
| | - Michael S Okun
- Fixel Center for Neurological Diseases, Program in Movement Disorders and Neurorestoration, Department of Neurology, University of Florida, Gainesville, FL, US
| | - Wissam Deeb
- Fixel Center for Neurological Diseases, Program in Movement Disorders and Neurorestoration, Department of Neurology, University of Florida, Gainesville, FL, US
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A retrospective evaluation of thalamic targeting for tremor deep brain stimulation using high-resolution anatomical imaging with supplementary fiber tractography. J Neurol Sci 2019; 398:148-156. [PMID: 30716581 DOI: 10.1016/j.jns.2019.01.025] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 12/22/2018] [Accepted: 01/15/2019] [Indexed: 12/25/2022]
Abstract
OBJECTIVES Deep brain stimulation (DBS) of the ventral intermediate (Vim) thalamic nucleus is used to treat tremors. Here, we identified the Vim nucleus on fast gray matter acquisition T1 inversion recovery (FGATIR) images and delineated the dentate-rubrothalamic tract (DRT) to determine the DBS target. We evaluated whether this method could consistently identify the Vim nucleus by anatomical imaging and fiber tractography. METHODS We retrospectively reviewed clinical data of patients who underwent unilateral thalamic DBS for severe tremor disorders. We evaluated outcomes at baseline, 6 months and 1 year following intervention, and annually thereafter. We reviewed preoperative planning to determine whether our tractography technique could consistently depict the DRT, and evaluated implanted electrode position by fusing postoperative CT scans to preoperative MR images. RESULTS Seven patients (three men and four women) were included; preoperative diagnoses included essential tremor (n = 3), Parkinson's (n = 2), and Holmes tremor (n = 2). All patients responded to DBS therapy; motor scores improved at 6-month and last follow-up. The Vim nucleus was successfully identified, as the DRT was depicted in all cases. Of ten active DBS contacts in seven leads, four contacts were located outside of the depicted DRT, and these contacts tended to require higher stimulation intensity. CONCLUSIONS The Vim nucleus was successfully identified with FGATIR. Our methods may be useful to determine optimal DBS trajectory, and potentially improve outcomes.
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20
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Müller EJ, Robinson PA. Suppression of Parkinsonian Beta Oscillations by Deep Brain Stimulation: Determination of Effective Protocols. Front Comput Neurosci 2018; 12:98. [PMID: 30618692 PMCID: PMC6297248 DOI: 10.3389/fncom.2018.00098] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Accepted: 11/26/2018] [Indexed: 01/05/2023] Open
Abstract
A neural field model of the corticothalamic-basal ganglia system is developed that describes enhanced beta activity within subthalamic and pallidal circuits in Parkinson's disease (PD) via system resonances. A model of deep brain stimulation (DBS) of typical clinical targets, the subthalamic nucleus (STN) and globus pallidus internus (GPi), is added and studied for several distinct stimulation protocols that are used for treatment of the motor symptoms of PD and that reduce pathological beta band activity (13-30 Hz) in the corticothalamic-basal ganglia network. The resulting impact of DBS on enhanced beta activity in the STN and GPi, as well as cortico-subthalamic and cortico-pallidal coherence, are studied. Both STN-DBS and GPi-DBS are found to be effective for suppressing peak STN and GPi power in the beta band, with GPi-DBS being slightly more effective in both the STN and the GPi for all stimulus protocols tested. The largest decrease in cortico-STN coherence is observed during STN-DBS, whereas GPi-DBS is most effective for reducing cortico-GPi coherence. A reduction of the pathologically large STN connection strengths that define the parkinsonian state results in enhanced 6 Hz activity and could thus represent a compensatory mechanism that has the side effect of driving parkinsonian tremor-like oscillations. This model provides a method for systematically testing effective DBS protocols that agrees with experimental and clinical findings. Furthermore, the model suggests GPi-DBS and STN-DBS have distinct impacts on elevated synchronization between the basal ganglia and motor cortex in PD.
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Affiliation(s)
- Eli J Müller
- School of Physics, The University of Sydney, Sydney, NSW, Australia.,Center for Integrative Brain Function, The University of Sydney, Sydney, NSW, Australia
| | - Peter A Robinson
- School of Physics, The University of Sydney, Sydney, NSW, Australia.,Center for Integrative Brain Function, The University of Sydney, Sydney, NSW, Australia
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Falconer RA, Rogers SL, Shenai M. Using Directional Deep Brain Stimulation to Co-activate the Subthalamic Nucleus and Zona Incerta for Overlapping Essential Tremor/Parkinson's Disease Symptoms. Front Neurol 2018; 9:544. [PMID: 30026728 PMCID: PMC6041971 DOI: 10.3389/fneur.2018.00544] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2018] [Accepted: 06/18/2018] [Indexed: 12/02/2022] Open
Abstract
This index case report describes a novel programming approach that utilizes the 8-contact directional Deep Brain Stimulation (DBS) lead to effectively control the akinesia, rigidity and tremor of Parkinson's Disease (PD), as well as a severe kinetic tremor of Essential Tremor (ET), in a patient with overlapping symptoms of both PD and ET. Through utilizing a bipolar directional montage on a single segmented contact, symptom control was attained via likely co-activation of the Subthalamic Nucleus (STN) and the adjacent Zona Incerta (ZI). The patient is a 67-year-old professional guitarist with a long-standing diagnosis of ET manifesting with bilateral kinetic tremor, who then developed right lateralizing symptoms indicative of PD. After optimal medical management did not confer sufficient control, he underwent left-sided unilateral DBS targeting the STN. Both intraoperatively and post-operatively, omnidirectional, and directional electrode review resulted in significant akinesia, rigidity, and as well as resting tremor control but failed to sufficiently improve the kinetic tremor. As electrode 2B was shown to be the most efficacious with the largest therapeutic window, a bipolar directional montage on a single segmented contact was tried with the idea of possibly further extending the axial asymmetry of the directional stimulation toward the adjacent ZI to impact the kinetic tremor. This montage resulted in full kinetic and resting tremor control as well as akinesia and rigidity response [2B cathode (–), 2A anode (+), 2C anode (+) (1.4 mA, rate 160 Hz, pulse width 60 μs)]. At 6 months post initial programming, no montage changes have been made, and the patient has experienced a reduction in Motor UPDRS scores from 23 to 3 (evaluated off medication), full resolution of kinetic tremor and normalization of handwriting, as well as significant reduction in his medication requirements. This patient's response to a single segment bipolar directional montage, and lack of response from monopolar directional stimulation in the same area, does suggest the possibility of further axial asymmetric tissue activation and thus co-activation of both the dorsal STN and adjacent ZI. Further modeling and study are warranted.
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Affiliation(s)
- Ramsey A Falconer
- Inova Parkinson's and Movement Disorders Center, Falls Church, VA, United States
| | - Sean L Rogers
- Inova Parkinson's and Movement Disorders Center, Falls Church, VA, United States
| | - Mahesh Shenai
- Inova Parkinson's and Movement Disorders Center, Falls Church, VA, United States
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22
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Objective predictors of 'early tolerance' to ventral intermediate nucleus of thalamus deep brain stimulation in essential tremor patients. Clin Neurophysiol 2018; 129:1628-1633. [PMID: 29908405 DOI: 10.1016/j.clinph.2018.05.012] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Revised: 04/24/2018] [Accepted: 05/04/2018] [Indexed: 01/08/2023]
Abstract
OBJECTIVE To identify pre-operative clinical and computerized spiral analysis characteristics that may help ascertain which patients with Essential Tremor (ET) will exhibit 'early tolerance' to ventral intermediate nucleus of thalamus (Vim) deep brain stimulation (DBS). METHODS Identification of comparative characteristics of defined cases of 'early tolerance' versus patients with sustained satisfactory response treated with Vim DBS surgery for medically-refractory ET, based on retrospective chart review by a clinician blinded to the findings of computerized spiral analysis. RESULTS Statistically significant differences in two spiral analysis indices, SWVI and DoS, were found in the dominant upper limbs of patients who developed 'early tolerance', whereas the clinical characteristics were not significantly different. CONCLUSION Objective measurements of upper limb kinematics using graphonomic tests like spiral analysis should be considered in the pre-operative evaluation for DBS, especially in the setting of moderate-severe predominantly action and proximal postural tremors. SIGNIFICANCE Ours is the first investigation looking into the pre-operative clinical and objective physiologic characteristics of the patients who develop 'early tolerance' to Vim DBS for the treatment of essential tremor. The study has significant implications for pre-operative evaluation and potential surgical target selection for the treatment of tremors.
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Abstract
INTRODUCTION Essential tremor is the most common form of pathologic tremor. Surgical therapies disrupt tremorogenic oscillation in the cerebellothalamocortical pathway and are capable of abolishing severe tremor that is refractory to available pharmacotherapies. Surgical methods are raspidly improving and are the subject of this review. Areas covered: A PubMed search on 18 January 2018 using the query essential tremor AND surgery produced 839 abstracts. 379 papers were selected for review of the methods, efficacy, safety and expense of stereotactic deep brain stimulation (DBS), stereotactic radiosurgery (SRS), focused ultrasound (FUS) ablation, and radiofrequency ablation of the cerebellothalamocortical pathway. Expert commentary: DBS and SRS, FUS and radiofrequency ablations are capable of reducing upper extremity tremor by more than 80% and are far more effective than any available drug. The main research questions at this time are: 1) the relative safety, efficacy, and expense of DBS, SRS, and FUS performed unilaterally and bilaterally; 2) the relative safety and efficacy of thalamic versus subthalamic targeting; 3) the relative safety and efficacy of atlas-based versus direct imaging tractography-based anatomical targeting; and 4) the need for intraoperative microelectrode recordings and macroelectrode stimulation in awake patients to identify the optimum anatomical target. Randomized controlled trials are needed.
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Affiliation(s)
- Rodger J Elble
- a Neuroscience Institute , Southern Illinois University School of Medicine , Springfield , Illinois , USA
| | - Ludy Shih
- b Department of Neurology , Beth Israel Deaconess Medical Center, Harvard Medical School , Boston , Massachusetts USA
| | - Jeffrey W Cozzens
- a Neuroscience Institute , Southern Illinois University School of Medicine , Springfield , Illinois , USA
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24
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Rodrigues NB, Mithani K, Meng Y, Lipsman N, Hamani C. The Emerging Role of Tractography in Deep Brain Stimulation: Basic Principles and Current Applications. Brain Sci 2018; 8:brainsci8020023. [PMID: 29382119 PMCID: PMC5836042 DOI: 10.3390/brainsci8020023] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2017] [Revised: 01/24/2018] [Accepted: 01/26/2018] [Indexed: 12/30/2022] Open
Abstract
Diffusion tensor imaging (DTI) is an MRI-based technique that delineates white matter tracts in the brain by tracking the diffusion of water in neural tissue. This methodology, known as “tractography”, has been extensively applied in clinical neuroscience to explore nervous system architecture and diseases. More recently, tractography has been used to assist with neurosurgical targeting in functional neurosurgery. This review provides an overview of DTI principles, and discusses current applications of tractography for improving and helping develop novel deep brain stimulation (DBS) targets.
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Affiliation(s)
- Nelson B Rodrigues
- Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
- Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
- Institute of Medical Sciences, University of Toronto, Toronto, ON M5S 1A8, Canada.
| | - Karim Mithani
- Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
- Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
| | - Ying Meng
- Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
- Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
- Institute of Medical Sciences, University of Toronto, Toronto, ON M5S 1A8, Canada.
| | - Nir Lipsman
- Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
- Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada.
| | - Clement Hamani
- Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada.
- Division of Neurosurgery, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON M4N 3M5, Canada.
- Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre, Toronto, ON M4N 3M5, Canada.
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Zsigmond P, Hemm-Ode S, Wårdell K. Optical Measurements during Deep Brain Stimulation Lead Implantation: Safety Aspects. Stereotact Funct Neurosurg 2018; 95:392-399. [DOI: 10.1159/000484944] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Accepted: 11/01/2017] [Indexed: 11/19/2022]
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Alloway KD, Smith JB, Mowery TM, Watson GDR. Sensory Processing in the Dorsolateral Striatum: The Contribution of Thalamostriatal Pathways. Front Syst Neurosci 2017; 11:53. [PMID: 28790899 PMCID: PMC5524679 DOI: 10.3389/fnsys.2017.00053] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Accepted: 07/07/2017] [Indexed: 01/24/2023] Open
Abstract
The dorsal striatum has two functionally-defined subdivisions: a dorsomedial striatum (DMS) region involved in mediating goal-directed behaviors that require conscious effort, and a dorsolateral striatum (DLS) region involved in the execution of habitual behaviors in a familiar sensory context. Consistent with its presumed role in forming stimulus-response (S-R) associations, neurons in DLS receive massive inputs from sensorimotor cortex and are responsive to both active and passive sensory stimulation. While several studies have established that corticostriatal inputs contribute to the stimulus-induced responses observed in the DLS, there is growing awareness that the thalamus has a significant role in conveying sensory-related information to DLS and other parts of the striatum. The thalamostriatal projections to DLS originate mainly from the caudal intralaminar region, which contains the parafascicular (Pf) nucleus, and from higher-order thalamic nuclei such as the medial part of the posterior (POm) nucleus. Based on recent findings, we hypothesize that the thalamostriatal projections from these two regions exert opposing influences on the expression of behavioral habits. This article reviews the subcortical circuits that regulate the transmission of sensory information through these thalamostriatal projection systems, and describes the evidence that indicates these circuits could be manipulated to ameliorate the symptoms of Parkinson's disease (PD) and related neurological disorders.
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Affiliation(s)
- Kevin D. Alloway
- Neural and Behavioral Sciences, Center for Neural Engineering, Pennsylvania State UniversityUniversity Park, PA, United States
| | - Jared B. Smith
- Molecular Neurobiology Laboratory, The Salk Institute for Biological StudiesLa Jolla, CA, United States
| | - Todd M. Mowery
- Center for Neural Science, New York UniversityNew York, NY, United States
| | - Glenn D. R. Watson
- Department of Psychology and Neuroscience, Duke UniversityDurham, NC, United States
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Deep brain stimulation of the centromedian thalamic nucleus for essential tremor: a case report. Acta Neurochir (Wien) 2017; 159:789-793. [PMID: 28303332 DOI: 10.1007/s00701-017-3143-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2016] [Accepted: 02/28/2017] [Indexed: 10/20/2022]
Abstract
The centromedian nucleus (CM) of the thalamus is an important site with anatomical connections to different cortical and subcortical motor areas; however, its role in tremor disorders is not clear, although deep brain stimulation (DBS) of the CM has been described to be effective in the treatment of parkinsonian tremor. We report a case of a patient with medication-refractory essential tremor (ET) who had excellent tremor suppression with DBS of the CM. The CM and the nearby region should be explored as a potential target for the treatment of ET and other forms of tremor.
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Rolston JD, Lim DA. In Reply: Thalamotomy-Like Effects from Partial Removal of a Ventral Intermediate Nucleus Deep Brain Stimulator Lead in a Patient With Essential Tremor. Neurosurgery 2017; 80:E256. [PMID: 28368504 DOI: 10.1093/neuros/nyx068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Affiliation(s)
- John D Rolston
- Department of Neurological Surgery University of California, San Francisco
| | - Daniel A Lim
- Department of Neurological Surgery University of California, San Francisco.,Surgical Service San Francisco Veterans Affairs Medical Center San Francisco, California
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29
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Ramirez-Zamora A, Smith H, Kumar V, Prusik J, Phookan S, Pilitsis JG. Evolving Concepts in Posterior Subthalamic Area Deep Brain Stimulation for Treatment of Tremor: Surgical Neuroanatomy and Practical Considerations. Stereotact Funct Neurosurg 2016; 94:283-297. [DOI: 10.1159/000449007] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2015] [Accepted: 08/08/2016] [Indexed: 11/19/2022]
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Rolston JD, Ramos AD, Heath S, Englot DJ, Lim DA. Thalamotomy-Like Effects From Partial Removal of a Ventral Intermediate Nucleus Deep Brain Stimulator Lead in a Patient With Essential Tremor: Case Report. Neurosurgery 2016. [PMID: 26200771 DOI: 10.1227/neu.0000000000000906] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND AND IMPORTANCE The ventral intermediate nucleus of the thalamus is a primary target of deep brain stimulation (DBS) in patients with essential tremor. Despite reliable control of contralateral tremor, there is sometimes a need for lead revision in cases of infection, hardware malfunction, or failure to relieve symptoms. Here, we present the case of a patient undergoing revision after ventral intermediate nucleus (Vim) DBS failed to control his tremor. During the electrode removal, the distal portion of the lead was found to be tightly adherent to tissue within the deep brain. Partial removal of the electrode in turn caused weakness, paresthesias, and tremor control similar to the effects produced by thalamotomy or thalamic injury. CLINICAL PRESENTATION A 48-year-old man with essential tremor had bilateral Vim DBS leads implanted 10 years earlier but had poor control of his tremor and ultimately opted for surgical revision with lead placement in the zona incerta. During attempted removal of his right lead, the patient became somnolent with contralateral weakness and paresthesias. The procedure was aborted, and postoperative neuroimaging was immediately obtained, showing no signs of stroke or hemorrhage. The patient had almost complete control of his left arm tremor postoperatively, and his weakness soon resolved. CONCLUSION To the best of our knowledge, this is the first reported case of cerebral injury after DBS revision and offers insights into the mechanism of high-frequency electric stimulation compared with lesions. That is, although high-frequency stimulation failed to control this patient's tremor, thalamotomy-like injury was completely effective.
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Affiliation(s)
- John D Rolston
- *Department of Neurological Surgery, University of California, San Francisco, California; ‡San Francisco VA Parkinson's Disease Research, Education, & Clinical Center and §Surgical Service, San Francisco Veterans Affairs Medical Center, San Francisco, California
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31
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García-Gomar MG, Soto-Abraham J, Velasco-Campos F, Concha L. Anatomic characterization of prelemniscal radiations by probabilistic tractography: implications in Parkinson's disease. Brain Struct Funct 2016; 222:71-81. [PMID: 26902343 DOI: 10.1007/s00429-016-1201-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Accepted: 02/09/2016] [Indexed: 12/19/2022]
Abstract
To characterize the anatomical connectivity of the prelemniscal radiations (Raprl), a white matter region within the posterior subthalamic area (PSA) that is an effective neurosurgical target for treating motor symptoms of Parkinson's disease (PD). Diffusion-weighted images were acquired from twelve healthy subjects using a 3T scanner. Constrained spherical deconvolution, a method that allows the distinction of crossing fibers within a voxel, was used to compute track-density images with sufficient resolution to accurately delineate distinct PSA regions and probabilistic tractography of Raprl in both hemispheres. Raprl connectivity was reproducible across all subjects and showed fibers traversing through this region towards primary and supplementary motor cortices, the orbitofrontal cortex, ventrolateral thalamus, and the globus pallidus, cerebellum and dorsal brainstem. All brain regions reached by Raprl fibers are part of motor circuits involved in the pathophysiology of PD; while these fiber systems converge at the level of the PSA, they can be spatially segregated. Fibers of distinct and specific motor control networks are identified within Raprl. The description of this anatomical crossroad suggests that, in the future, tractography could allow deep brain stimulation or lesional therapies in white matter targets according to individual patient's symptoms.
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Affiliation(s)
| | - Julian Soto-Abraham
- Unit for Stereotactic and Functional Neurosurgery and Radiosurgery, Mexico General Hospital, Mexico City, Mexico
| | - Francisco Velasco-Campos
- Unit for Stereotactic and Functional Neurosurgery and Radiosurgery, Mexico General Hospital, Mexico City, Mexico
| | - Luis Concha
- Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro, México.
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Sandström L, Hägglund P, Johansson L, Blomstedt P, Karlsson F. Speech intelligibility in Parkinson's disease patients with zona incerta deep brain stimulation. Brain Behav 2015; 5:e00394. [PMID: 26516614 PMCID: PMC4614054 DOI: 10.1002/brb3.394] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Revised: 07/06/2015] [Accepted: 08/16/2015] [Indexed: 11/08/2022] Open
Abstract
OBJECTIVES To investigate the effects of l-dopa (Levodopa) and cZi-DBS (deep brain stimulation in caudal zona incerta) on spontaneous speech intelligibility in patients with PD (Parkinson's disease). MATERIALS AND METHODS Spontaneous utterances were extracted from anechoic recordings from 11 patients with PD preoperatively (off and on l-dopa medication) and 6 and 12 months post bilateral cZi-DBS operation (off and on stimulation, with simultaneous l-dopa medication). Background noise with an amplitude corresponding to a clinical setting was added to the recordings. Intelligibility was assessed through a transcription task performed by 41 listeners in a randomized and blinded procedure. RESULTS A group-level worsening in spontaneous speech intelligibility was observed on cZi stimulation compared to off 6 months postoperatively (8 adverse, 1 positive, 2 no change). Twelve months postoperatively, adverse effects of cZi-DBS were not frequently observed (2 positive, 3 adverse, 6 no change). l-dopa administered preoperatively as part of the evaluation for DBS operation provided the overall best treatment outcome (1 adverse, 4 positive, 6 no change). CONCLUSIONS cZi-DBS was shown to have smaller negative effects when evaluated from spontaneous speech compared to speech effects reported previously. The previously reported reduction in word-level intelligibility 12 months postoperatively was not transferred to spontaneous speech for most patients. Reduced intelligibility due to cZi stimulation was much more prominent 6 months postoperatively than at 12 months.
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Affiliation(s)
- Linda Sandström
- Division of Speech and Language PathologyDepartment of Clinical SciencesUmeå UniversityUmeåSweden
| | - Patricia Hägglund
- Division of Speech and Language PathologyDepartment of Clinical SciencesUmeå UniversityUmeåSweden
| | - Louise Johansson
- Division of Speech and Language PathologyDepartment of Clinical SciencesUmeå UniversityUmeåSweden
| | - Patric Blomstedt
- Division of Clinical NeuroscienceDepartment of Pharmacology and Clinical NeuroscienceUmeå UniversityUmeåSweden
| | - Fredrik Karlsson
- Division of Speech and Language PathologyDepartment of Clinical SciencesUmeå UniversityUmeåSweden
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News and controversies regarding essential tremor. Rev Neurol (Paris) 2015; 171:415-25. [DOI: 10.1016/j.neurol.2015.02.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2014] [Revised: 02/01/2015] [Accepted: 02/02/2015] [Indexed: 01/08/2023]
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Fuller CJ, Misbahuddin A, Prezerakos G, Haliasos N, Low H. Comment on the Article by Ledermann et al. Entitled ‘Effects of Cerebellothalamic Tractotomy on Cognitive and Emotional Functioning in Essential Tremor: A Preliminary Study in 5 Essential Tremor Patients'. Stereotact Funct Neurosurg 2015; 93:378-9. [DOI: 10.1159/000440728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Accepted: 08/31/2015] [Indexed: 11/19/2022]
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Abstract
Deep brain stimulation of the thalamus (and especially the ventral intermediate nucleus) does not significantly improve a drug-resistant, disabling cerebellar tremor. The dentato-rubro-olivary tract (Guillain-Mollaret triangle, including the red nucleus) is a subcortical loop that is critically involved in tremor genesis. We report the case of a 48-year-old female patient presenting with generalized cerebellar tremor caused by alcohol-related cerebellar degeneration. Resistance to pharmacological treatment and the severity of the symptoms prompted us to investigate the effects of bilateral deep brain stimulation of the red nucleus. Intra-operative microrecordings of the red nucleus revealed intense, irregular, tonic background activity but no rhythmic components that were synchronous with upper limb tremor. The postural component of the cerebellar tremor disappeared during insertion of the macro-electrodes and for a few minutes after stimulation, with no changes in the intentional (kinetic) component. Stimulation per se did not reduce postural or intentional tremor and was associated with dysautonomic symptoms (the voltage threshold for which was inversed related to the stimulation frequency). Our observations suggest that the red nucleus is (1) an important centre for the genesis of cerebellar tremor and thus (2) a possible target for drug-refractory tremor. Future research must determine how neuromodulation of the red nucleus can best be implemented in patients with cerebellar degeneration.
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36
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Bendersky D, Ajler P, Yampolsky C. [The use of neuromodulation for the treatment of tremor]. Surg Neurol Int 2014; 5:S232-46. [PMID: 25165613 PMCID: PMC4138824 DOI: 10.4103/2152-7806.137944] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2012] [Accepted: 11/29/2012] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND Tremor may be a disabling disorder and pharmacologic treatment is the first-line therapy for these patients. Nevertheless, this treatment may lead to a satisfactory tremor reduction in only 50% of patients with essential tremor. Thalamotomy was the treatment of choice for tremor refractory to medical therapy until deep brain stimulation (DBS) of the ventral intermedius nucleus (Vim) of the thalamus has started being used. Nowadays, thalamotomy is rarely performed. METHODS This article is a non-systematic review of the indications, results, programming parameters and surgical technique of DBS of the Vim for the treatment of tremor. RESULTS In spite of the fact that it is possible to achieve similar clinical results using thalamotomy or DBS of the Vim, the former causes more adverse effects than the latter. Furthermore, DBS can be used bilaterally, whereas thalamotomy has a high risk of causing disartria when it is performed in both sides. DBS of the Vim achieved an adequate tremor improvement in several series of patients with tremor caused by essential tremor, Parkinson's disease or multiple sclerosis. Besides the Vim, there are other targets, which are being used by some authors, such as the zona incerta and the prelemniscal radiations. CONCLUSION DBS of the Vim is a useful treatment for disabling tremor refractory to medical therapy. It is essential to carry out an accurate patient selection as well as to use a proper surgical technique. The best stereotactic target for tremor is still unknown, although the Vim is the most used one.
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Affiliation(s)
- Damián Bendersky
- Department of Neurosurgery, Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
| | - Pablo Ajler
- Department of Neurosurgery, Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
| | - Claudio Yampolsky
- Department of Neurosurgery, Hospital Italiano de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina
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37
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Kalia SK, Sankar T, Lozano AM. Deep brain stimulation for Parkinson's disease and other movement disorders. Curr Opin Neurol 2014; 26:374-80. [PMID: 23817213 DOI: 10.1097/wco.0b013e3283632d08] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW Deep brain stimulation (DBS) is now widely used in the treatment of Parkinson's disease, tremor, and dystonia. This review examines recent developments in the application of DBS to the management of movement disorders. RECENT FINDINGS In Parkinson's disease, recent work has demonstrated that early DBS may have a significant benefit on quality of life and motor symptoms while permitting a decrease in levodopa equivalent dosage. Thalamic DBS continues to be a well established target for the treatment of tremor, although recent work suggests that alternative targets such as the posterior subthalamic area may be similarly efficacious. The treatment of primary dystonia with DBS has been established in multiple recent trials, demonstrating prolonged symptomatic benefit. SUMMARY DBS is now an established symptomatic treatment modality for Parkinson's disease and other movement disorders. Future work will undoubtedly involve establishing new indications and targets in the treatment of movement disorders with further refinements to existing technology. Ultimately, these methods combined with biologically based therapies may catalyze a shift from symptomatic treatment to actually modifying the natural history of neurodegenerative diseases such as Parkinson's disease.
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Affiliation(s)
- Suneil K Kalia
- Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada
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38
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Anderson D, Kartha N. Deep Brain Stimulation in Nonparkinsonian Movement Disorders and Emerging Technologies, Targets, and Therapeutic Promises in Deep Brain Stimulation. Neurol Clin 2013; 31:809-26. [DOI: 10.1016/j.ncl.2013.03.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Brücke C, Bock A, Huebl J, Krauss JK, Schönecker T, Schneider GH, Brown P, Kühn AA. Thalamic gamma oscillations correlate with reaction time in a Go/noGo task in patients with essential tremor. Neuroimage 2013; 75:36-45. [PMID: 23466935 DOI: 10.1016/j.neuroimage.2013.02.038] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2012] [Revised: 01/23/2013] [Accepted: 02/14/2013] [Indexed: 10/27/2022] Open
Abstract
Intracerebral recordings of neuronal activity in patients undergoing deep brain stimulation have revealed characteristic movement-related desynchronization at frequencies <30 Hz and increased activity in the gamma band (~30-100 Hz) in the basal ganglia and thalamus. Thalamic gamma activity is also found during arousal. Here, we explore oscillatory gamma band activity recorded from the ventralis intermedius nucleus of the thalamus during motor performance in a Go/noGo task in 10 patients with essential tremor after implantation of deep brain stimulation electrodes. We show that movement-related gamma activity is lateralized to the nucleus contralateral to the moved side similar to previous findings in the globus pallidus internus and the subthalamic nucleus. The onset of contralateral gamma band synchronization following imperative Go cues is positively correlated with reaction time. Remarkably, baseline levels of gamma activity shortly before the Go cue correlated with the reaction times. Here, faster responses occurred in patients with higher levels of pre-cue gamma activity. Our findings support the role of gamma activity as a physiological prokinetic activity in the motor system. Moreover, we suggest that subtle fluctuations in pre-cue gamma band activity may have an impact on task performance and may index arousal-related states.
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Affiliation(s)
- Christof Brücke
- Department of Neurology, Charité - Universitätsmedizin Berlin, Germany
| | - Antje Bock
- Department of Neurology, Charité - Universitätsmedizin Berlin, Germany
| | - Julius Huebl
- Department of Neurology, Charité - Universitätsmedizin Berlin, Germany
| | - Joachim K Krauss
- Department of Neurosurgery, Medizinische Hochschule Hannover, Germany
| | - Thomas Schönecker
- Department of Neurology, Charité - Universitätsmedizin Berlin, Germany
| | | | - Peter Brown
- Nuffield Department of Clinical Neurology, University Oxford, UK
| | - Andrea A Kühn
- Department of Neurology, Charité - Universitätsmedizin Berlin, Germany.
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Kerl HU, Gerigk L, Brockmann MA, Huck S, Al-Zghloul M, Groden C, Hauser T, Nagel AM, Nölte IS. Imaging for deep brain stimulation: The zona incerta at 7 Tesla. World J Radiol 2013; 5:5-16. [PMID: 23494089 PMCID: PMC3596566 DOI: 10.4329/wjr.v5.i1.5] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2012] [Revised: 10/24/2012] [Accepted: 01/21/2013] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate different promising magnetic resonance imaging (MRI) methods at 7.0 Tesla (T) for the pre-stereotactic visualization of the zona incerta (ZI).
METHODS: Two neuroradiologists qualitatively and quantitatively examined T2-turbo spin-echo (T2-TSE), T1-weighted gradient-echo, as well as FLASH2D-T2Star and susceptibility-weighted imaging (SWI) for the visualization of the ZI at 7.0 T MRI. Delineation and image quality for the ZI were independently examined using a 6-scale grading system. Inter-rater reliability using Cohen’s kappa coefficient (κ) were assessed. Contrast-to-noise ratios (CNR), and signal-to-noise ratios (SNR) for the ZI were calculated for all sequences. Differences in delineation, SNR, and CNR between the sequences were statistically assessed using a paired t-test. For the anatomic validation the coronal FLASH2D-T2Star images were co-registered with a stereotactic atlas (Schaltenbrand-Wahren).
RESULTS: The rostral part of the ZI (rZI) could easily be identified and was best and reliably visualized in the coronal FLASH2D-T2Star images. The caudal part was not definable in any of the sequences. No major artifacts in the rZI were observed in any of the scans. FLASH2D-T2Star and SWI imaging offered significant higher CNR values for the rZI compared to T2-TSE images (P > 0.05). The co-registration of the coronal FLASH2D-T2Star images with the stereotactic atlas schema (Schaltenbrand-Wahren) confirmed the correct localization of the ZI in all cases.
CONCLUSION: FLASH2D-T2Star imaging (particularly coronal view) provides the reliable and currently optimal visualization of the rZI at 7.0 T. These results can facilitate a better and more precise targeting of the caudal part of the ZI than ever before.
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Abstract
Essential tremor is the most common tremor disorder and is characterized by a postural and kinetic tremor. Most commonly, the disease involves the upper extremities, although other body parts may be affected. Essential tremor is seen most often in adults and may markedly limit abilities to perform daily activities. Medications often fail to control the tremor adequately. In the past, ventral intermediate nucleus of the thalamus (VIM) thalamotomy was the surgery of choice for medication-resistant patients with disabling tremor. With technological advances, deep brain stimulation (DBS) to the VIM has replaced thalamotomy as the operation of choice for patients with essential tremor, given the heightened risk of permanent neurological deficits associated with ablative surgery. Multiple studies have demonstrated that unilateral VIM DBS has significant short- and long-term benefits for targeted tremor. Unilateral VIM DBS may also improve head and voice tremor, although most commonly bilateral stimulation is required for adequate control. However, bilateral thalamic stimulation is associated with a higher incidence of neurological deficits, particularly speech and gait problems. Investigations of DBS of other brain target areas for essential tremor, such as the posterior subthalamic area and the subthalamic nucleus, are ongoing.
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Affiliation(s)
- Jules M Nazzaro
- Department of Neurosurgery, University of Kansas Medical Center, Kansas City, KS, USA; Department of Neurology, University of Kansas Medical Center, Kansas City, KS, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS, USA
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Abosch A, Timmermann L, Bartley S, Rietkerk HG, Whiting D, Connolly PJ, Lanctin D, Hariz MI. An International Survey of Deep Brain Stimulation Procedural Steps. Stereotact Funct Neurosurg 2012; 91:1-11. [DOI: 10.1159/000343207] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2012] [Accepted: 09/01/2012] [Indexed: 11/19/2022]
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Lefranc M, Le Gars D. Robotic implantation of deep brain stimulation leads, assisted by intra-operative, flat-panel CT. Acta Neurochir (Wien) 2012; 154:2069-74. [PMID: 22814648 DOI: 10.1007/s00701-012-1445-7] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2012] [Accepted: 07/04/2012] [Indexed: 12/01/2022]
Abstract
BACKGROUND There are two mandatory skills in deep brain stimulation (DBS) neurosurgery: accuracy and control. METHOD Frame-based robotic registration was performed. Prior to insertion into the skull, the guide tube's position was checked with flat-panel computed tomography (fpCT). After registration against the pre-operative plan, we measured and corrected the robotic arm's position so that the guide tube with the micro-electrode would follow the planned trajectory exactly. We then used fpCT again to check the DBS lead's final position. CONCLUSION The combination of intra-operative fpCT with robotised surgery provides an appropriate, user-friendly solution to the key technical challenges in DBS lead implantation.
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Affiliation(s)
- M Lefranc
- Neurosurgery Department, Amiens University Hospital, 5 place Victor Pauchet, 80054, Amiens cedex 1, France.
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Post subthalamic area deep brain stimulation for tremors: a mini-review. Transl Neurodegener 2012; 1:20. [PMID: 23210767 PMCID: PMC3534556 DOI: 10.1186/2047-9158-1-20] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2012] [Accepted: 10/06/2012] [Indexed: 11/24/2022] Open
Abstract
Deep brain stimulation (DBS) in the thalamic ventrointermediate nucleus (VIM) is the traditional target for the surgical treatment of pharmacologically refractory essential tremor or parkinsonian tremor. Studies in recent years on DBS in posterior subthalamic area (PSA), including the zona incerta and the prelemniscal radiation, have shown promising results in tremor suppression, particularly for those tremors difficult to be well controlled by VIM DBS, such as the proximal postural tremor, distal intention tremor and some cerebellar outflow tremor in various diseases including essential tremor and multiple sclerosis. The adverse effect profile of the PSA DBS is mild and transient, without lasting or striking dysarthria, disequilibrium or tolerance, in contrast to VIM DBS, particularly bilateral DBS. However, the studies on PSA DBS so far are still limited, with a handful of studies on bilateral PSA, and a short follow up duration compared to VIM. More studies are needed for direct comparison of these targets in the future. A review here would help to gain more insight into the benefits and limits of the PSA DBS compared to that in VIM in the clinical management of various tremors, particularly for those difficult to be well controlled by traditional VIM DBS.
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Keane M, Deyo S, Abosch A, Bajwa JA, Johnson MD. Improved spatial targeting with directionally segmented deep brain stimulation leads for treating essential tremor. J Neural Eng 2012; 9:046005. [PMID: 22732947 DOI: 10.1088/1741-2560/9/4/046005] [Citation(s) in RCA: 71] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Deep brain stimulation (DBS) in the ventral intermediate nucleus of thalamus (Vim) is known to exert a therapeutic effect on postural and kinetic tremor in patients with essential tremor (ET). For DBS leads implanted near the caudal border of Vim, however, there is an increased likelihood that one will also induce paresthesia side-effects by stimulating neurons within the sensory pathway of the ventral caudal (Vc) nucleus of thalamus. The aim of this computational study was to (1) investigate the neuronal pathways modulated by therapeutic, sub-therapeutic and paresthesia-inducing DBS settings in three patients with ET and (2) determine how much better an outcome could have been achieved had these patients been implanted with a DBS lead containing directionally segmented electrodes (dDBS). Multi-compartment neuron models of the thalamocortical, cerebellothalamic and medial lemniscal pathways were first simulated in the context of patient-specific anatomies, lead placements and programming parameters from three ET patients who had been implanted with Medtronic 3389 DBS leads. The models showed that in these patients, complete suppression of tremor was associated most closely with activating an average of 62% of the cerebellothalamic afferent input into Vim (n = 10), while persistent paresthesias were associated with activating 35% of the medial lemniscal tract input into Vc thalamus (n = 12). The dDBS lead design demonstrated superior targeting of the cerebello-thalamo-cortical pathway, especially in cases of misaligned DBS leads. Given the close proximity of Vim to Vc thalamus, the models suggest that dDBS will enable clinicians to more effectively sculpt current through and around thalamus in order to achieve a more consistent therapeutic effect without inducing side-effects.
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Affiliation(s)
- Maureen Keane
- Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN, USA
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Visualisation of the zona incerta for deep brain stimulation at 3.0 Tesla. Clin Neuroradiol 2012; 22:55-68. [PMID: 22349435 DOI: 10.1007/s00062-012-0136-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2011] [Accepted: 01/27/2012] [Indexed: 12/23/2022]
Abstract
PURPOSE Deep-brain stimulation (DBS) of the zona incerta (ZI) has shown promising results for medication-refractory neurological disorders including Parkinson's disease (PD) and essential tremor (ET). The success of the intervention is indispensably dependent on the reliable visualisation of the ZI. The aim of the study was to evaluate different promising new magnetic resonance imaging (MRI) methods at 3.0 Tesla for pre-stereotactic visualisation of the ZI using a standard installation the protocol. METHODS MRI of nine healthy volunteers was acquired (T1-MPRAGE, T2-FLAIR, T2*-FLASH2D, T2-SPACE and susceptibility-weighted imaging (SWI). Image quality and visualisation of the ZI for each sequence were analysed independently by two neuroradiologists using a 6-point scale. For T2*-FLASH2D the axial, coronal and sagittal planes were compared. The delineation of the ZI versus the internal capsule, the subthalamic nucleus and the pallidofugal fibres was evaluated in all sequences and compared to T2-FLAIR using a paired t-test. Inter-rater reliability, contrast-to-noise ratios (CNR), and signal-to-noise ratios (SNR) for the ZI were computed. For illustration, coronal T2*-FLASH2D images were co-registered with the corresponding section schema of the Schaltenbrand-Wahren stereotactic atlas. RESULTS Only the rostral part of the ZI (rZI) could be identified. The rZI was best and reliably visualised in T2*-FLASH2D (particularly coronal orientation; p < 0.05). No major artifacts in the rZI were observed in any of the sequences. SWI, T2-SPACE, and T2*-FLASH imaging offered significant higher CNR values for the rZI compared to T2-FLAIR imaging using standard parameters. The co-registration of the coronal T2*-FLASH2D images projected the ZI clearly into the boundaries of the anatomical sections. CONCLUSIONS The delineation of the rZI is best possible in T2*-FLASH2D (particularly coronal view) using a standard installation protocol at 3.0 T. The caudal ZI could not be discerned in any of the sequences.
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Lozano AM, Levy R. Reoperation of deep brain stimulation in patients with essential tremor. World Neurosurg 2012; 78:442-4. [PMID: 22373891 DOI: 10.1016/j.wneu.2012.01.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2012] [Accepted: 01/12/2012] [Indexed: 11/26/2022]
Affiliation(s)
- Andres M Lozano
- Division of Neurosurgery, Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada.
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