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Sarica C, Yamamoto K, Iorio-Morin C, Germann J, Yang AZ, Santyr B, Colditz M, Vetkas A, Fomenko A, Davidson B, Schmidt F, Grippe T, Samuel N, Zemmar A, Flouty O, Cheyuo C, Darmani G, Chen R, Boutet A, Neudorfer C, Hodaie M, Kalia SK, Munhoz RP, Fasano A, Lozano AM. Bilateral Focused Ultrasound Thalamotomy for Essential Tremor: Clinical Outcomes Compared to Bilateral Deep Brain Stimulation and Probabilistic Lesion Mapping. Mov Disord 2025. [PMID: 40318052 DOI: 10.1002/mds.30221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 04/02/2025] [Accepted: 04/15/2025] [Indexed: 05/07/2025] Open
Abstract
BACKGROUND The efficacy and adverse events (AEs) of bilateral magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomies for essential tremor (ET) have not been compared to those of deep brain stimulation (DBS). Furthermore, it is uncertain whether second-side thalamotomies can be positioned differently from the first without compromising effectiveness. OBJECTIVE We aimed to indirectly compare bilateral MRgFUS and DBS, while identifying optimal lesion/stimulation locations. METHODS We retrospectively examined 41 ET patients who received either bilateral thalamic DBS (n = 22) or MRgFUS (n = 19) surgery. The primary outcome was the comparison of modalities for change in Clinical Rating Scale for Tremor (CRST) from baseline to post second surgery. We characterized AEs, generated probabilistic maps, and tracked streamlines intersecting lesions. First-side lesions were always intentionally placed ventrally (z = 0/+2 mm above the intercommissural plane [ICP]), and second-side lesions were placed dorsally (z = +3 mm above ICP). RESULTS Tremor scores improved significantly after second surgeries (MRgFUS: 56.3 ± 7.1 to 24.2 ± 10.4, P < 0.001; DBS: 58.8 ± 11.6 to 25.0 ± 13, P < 0.05, mean follow-up: 23/26 months), with no differences between modalities. Following first surgeries, scores were MRgFUS: 37.9 ± 7.9 and DBS: 35.2 ± 13.6, with significant improvement from baseline (P < 0.001, mean follow-up: 40/73 months). All AEs were grade 1-2, with AE-free rates of 41% for DBS and 32% for MRgFUS. First-side lesions exhibited maximal efficacy in the ventral Vim, extending to posterior subthalamic area (PSA), whereas second-side lesions demonstrated maximal efficacy in the dorsomedial Vim-Vop border. DBS maps corroborated this finding and confined to Vim-Vop border. Lesions intersecting with networks interconnected with the supplementary motor area, in addition to M1, were associated with improved outcomes. CONCLUSIONS The efficacies of bilateral MRgFUS and DBS appear comparable. MRgFUS probabilistic maps vary with different targeting methods, revealing two distinct sweet spots: dorsal Vim-Vop border and ventral Vim/PSA. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Can Sarica
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Kazuaki Yamamoto
- Functional Neurosurgery Center, Shonan Fujisawa Tokushukai Hospital, Fujisawa, Japan
| | - Christian Iorio-Morin
- Division of Neurosurgery, Department of Surgery, Université de Sherbrooke, Sherbrooke, Quebec, Canada
| | - Jurgen Germann
- Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
- Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Ontario, Canada
| | - Andrew Z Yang
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Brendan Santyr
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Michael Colditz
- School of Medicine, University of Queensland, Brisbane, Queensland, Australia
| | - Artur Vetkas
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Department of Neurosurgery, Tartu University Hospital, Tartu, Estonia
| | - Anton Fomenko
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Benjamin Davidson
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Franziska Schmidt
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
| | - Talyta Grippe
- Edmond J. Safra Program in Parkinson's Disease Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, and Division of Neurology, University of Toronto, Toronto, Ontario, Canada
| | - Nardin Samuel
- Edmond J. Safra Program in Parkinson's Disease Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, and Division of Neurology, University of Toronto, Toronto, Ontario, Canada
| | - Ajmal Zemmar
- Department of Neurological Surgery, University of Louisville School of Medicine, Louisville, Kentucky, USA
| | - Oliver Flouty
- Department of Neurosurgery and Brain Repair, Tampa Neurophysiology Laboratory, University of South Florida, Tampa, Florida, USA
| | - Cletus Cheyuo
- Department of Neurosurgery, Lahey Hospital and Medical Center, Burlington, Massachusetts, USA
| | - Ghazaleh Darmani
- Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
| | - Robert Chen
- Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
- Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Ontario, Canada
- Edmond J. Safra Program in Parkinson's Disease Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, and Division of Neurology, University of Toronto, Toronto, Ontario, Canada
| | - Alexandre Boutet
- Joint Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada
| | - Clemens Neudorfer
- Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Mojgan Hodaie
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
- Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Ontario, Canada
| | - Suneil K Kalia
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
- Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Ontario, Canada
- KITE, University Health Network, Toronto, Ontario, Canada
| | - Renato P Munhoz
- Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
- Edmond J. Safra Program in Parkinson's Disease Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, and Division of Neurology, University of Toronto, Toronto, Ontario, Canada
| | - Alfonso Fasano
- Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
- Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Ontario, Canada
- Edmond J. Safra Program in Parkinson's Disease Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, and Division of Neurology, University of Toronto, Toronto, Ontario, Canada
- KITE, University Health Network, Toronto, Ontario, Canada
| | - Andres M Lozano
- Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada
- Krembil Research Institute, University Health Network, Toronto, Ontario, Canada
- Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Ontario, Canada
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Bulut E, Johansen PM, Elbualy A, Kalman C, Mayer R, Kato N, Salmeron de Toledo Aguiar R, Pilitsis JG. How Long Does Deep Brain Stimulation Give Patients Benefit? Neuromodulation 2025; 28:472-483. [PMID: 39001725 DOI: 10.1016/j.neurom.2024.05.007] [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: 12/19/2023] [Revised: 05/01/2024] [Accepted: 05/22/2024] [Indexed: 07/15/2024]
Abstract
INTRODUCTION One of the most common questions patients ask when they are contemplating deep brain stimulation (DBS) is how long it will last. To guide physicians in answering this query, we performed a scoping review to assess the current state of the literature and to identify the gaps that need to be addressed. MATERIALS AND METHODS The authors performed a MEDLINE search inclusive of articles from January 1987 (advent of DBS literature) to June 2023 including human and modeling studies written in English. For longevity of therapy data, only studies with a mean follow-up of ≥three years were included. Using the Rayyan platform, two reviewers (JP and RM) performed a title screen. Of the 734 articles, 205 were selected by title screen and 109 from abstract review. Ultimately, a total of 122 articles were reviewed. The research questions we explored were 1) how long can the different components of the DBS system maintain functionality? and 2) how long can DBS remain efficacious in treating Parkinson's disease (PD), essential tremor (ET), dystonia, and other disorders? RESULTS We showed that patients with PD, ET, and dystonia maintain a considerable long-term benefit in motor scores seven to ten years after implant, although the percentage improvement decreases over time. Stimulation off scores in PD and ET show worsening, consistent with disease progression. Battery life varies by the disease treated and the programming settings used. There remains a paucity of literature after ten years, and the impact of new device technology has not been classified to date. CONCLUSION We reviewed existing data on DBS longevity. Overall, outcomes data after ten years of therapy are substantially limited in the current literature. We recommend that physicians who have data for patients with DBS exceeding this duration publish their results.
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Affiliation(s)
- Esin Bulut
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA
| | - P Mitchell Johansen
- Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, USA
| | - Alya Elbualy
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA
| | - Cheyenne Kalman
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA
| | - Ryan Mayer
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA
| | - Nicholas Kato
- Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA
| | | | - Julie G Pilitsis
- Department of Neurosurgery, University of Arizona, Tucson, AZ, USA.
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Reese R, Koeglsperger T, Schrader C, Tönges L, Deuschl G, Kühn AA, Krack P, Schnitzler A, Storch A, Trenkwalder C, Höglinger GU. Invasive therapies for Parkinson's disease: an adapted excerpt from the guidelines of the German Society of Neurology. J Neurol 2025; 272:219. [PMID: 39985674 PMCID: PMC11846738 DOI: 10.1007/s00415-025-12915-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2024] [Revised: 01/07/2025] [Accepted: 01/12/2025] [Indexed: 02/24/2025]
Abstract
BACKGROUND Parkinson's disease (PD) is characterized by hypokinetic motor symptoms, tremor, and various non-motor symptoms with frequent fluctuations of symptoms in advanced disease stages. Invasive therapies, such as deep brain stimulation (DBS), ablative therapies, and continuous subcutaneous or intrajejunal delivery of dopaminergic drugs via pump therapies are available for the management of this complex motor symptomatology and may also impact non-motor symptoms. The recent update of the clinical guideline on PD by the German Neurological Society (Deutsche Gesellschaft für Neurologie e.V.; DGN) offers clear guidance on the indications and applications of these treatment options. METHODS The guideline committee formulated diagnostic questions for invasive therapies and structured them according to the PICOS framework (Population-Intervention-Comparisons-Outcome-Studies). A systematic literature review was conducted. Questions were addressed using the findings from the literature review and consented by the guideline committee. RESULTS Specific recommendations are given regarding (i) the optimal timing for starting invasive therapies, (ii) the application of DBS, (iii) the use of pump therapies in advanced PD, (iv) the indications for ablative procedures, and (iv) selecting the most appropriate therapy according to individual patient characteristics. CONCLUSION This review is an adapted excerpt of the chapters on the use of invasive therapies in PD of the novel German guideline on PD. Clear recommendations on the use of treatment options for advanced PD are provided.
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Affiliation(s)
- René Reese
- Department of Neurology, Rostock University Medical Center, Rostock, Germany.
- Klinik und Poliklinik für Neurologie, Universitätsmedizin Rostock, Gehlsheimer Str. 20, 18147, Rostock, Germany.
| | - Thomas Koeglsperger
- Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany
- German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Rostock, Germany
| | | | - Lars Tönges
- Department of Neurology, St. Josef-Hospital, Ruhr University Bochum, Bochum, Germany
- Neurodegeneration Research, Protein Research Unit Ruhr (PURE), Ruhr University Bochum, Bochum, Germany
| | - Günther Deuschl
- Department of Neurology, University Hospital Schleswig-Holstein, Kiel, Germany
| | - Andrea A Kühn
- Movement Disorder and Neuromodulation Unit, Department of Neurology, Charité, University Medicine Berlin, Berlin, Germany
| | - Paul Krack
- Movement Disorders Center, Department of Neurology, University Hospital (Inselspital) and University of Bern, Bern, Switzerland
| | - Alfons Schnitzler
- Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
- Department of Neurology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany
| | - Alexander Storch
- Department of Neurology, Rostock University Medical Center, Rostock, Germany
- Center for Transdisciplinary Neurosciences Rostock (CTNR), Rostock University Medical Center, Rostock, Germany
- German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Rostock, Germany
| | - Claudia Trenkwalder
- Paracelsus-Elena-Klinik, Kassel, Germany
- Department of Neurosurgery, University Medical Center Göttingen, Göttingen, Germany
| | - Günter U Höglinger
- Department of Neurology, LMU University Hospital, LMU Munich, Munich, Germany
- German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
- Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
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Shaikhouni A, Brandon C, Criss C. Bridging the Gap in FDA Approval for Pediatric Neuromodulation Devices. CHILDREN (BASEL, SWITZERLAND) 2025; 12:148. [PMID: 40003250 PMCID: PMC11853837 DOI: 10.3390/children12020148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Revised: 12/30/2024] [Accepted: 01/08/2025] [Indexed: 02/27/2025]
Abstract
While neuromodulation devices for managing neurological conditions have significantly advanced, there remains a substantial gap in FDA-approved devices specifically designed for pediatric patients. Devices like deep brain stimulators (DBS), vagus nerve stimulators (VNS), and spinal cord stimulators (SCS) are primarily approved for adults, with few options for children. To meet pediatric needs, off-label use is common; however, unique challenges to pediatric device development-such as ethical concerns, small trial populations, and financial disincentives due to the limited market size-continue to hinder progress. This review examines these barriers to pediatric neuromodulation device development and FDA (Food and Drug Administration) approval, as well as the current efforts, such as FDA initiatives and consortia support, that address regulatory and financial challenges. Furthermore, we discuss pathways like the Humanitarian Device Exemptions and Real-World Evidence programs that aim to streamline the approval process and address unmet clinical needs in pediatric care. Addressing these barriers could expand access to effective neuromodulation treatments and improve patient care.
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Affiliation(s)
- Ammar Shaikhouni
- Division of Pediatric Neurosurgery, Nationwide Children’s Hospital, 700 Children’s Dr., Columbus, OH 43205, USA
- Department of Neurological Surgery, The Ohio State University Medical Center, Columbus, OH 43210, USA;
| | - Cameron Brandon
- Department of Neurological Surgery, The Ohio State University Medical Center, Columbus, OH 43210, USA;
| | - Cory Criss
- Section of Pediatric Surgery, Department of Surgery, Nationwide Children’s Hospital, 700 Children’s Dr., Columbus, OH 43205, USA;
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Harland T, Sabourin S, Mayer R, Durphy J, Adam O, Pilitsis JG. Longevity of Deep Brain Stimulation in Essential Tremor: A Comparison of Omnidirectional and Directional Leads. Neurosurgery 2024:00006123-990000000-01474. [PMID: 39665529 DOI: 10.1227/neu.0000000000003308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 10/24/2024] [Indexed: 12/13/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Patients undergoing thalamic ventral intermediate nucleus stimulation to treat essential tremor (ET) develop tolerance over time, requiring higher stimulation amplitudes that lead to more frequent battery changes and suboptimal tremor control. The study objective is to determine whether amplitude tolerance differs between patients with omnidirectional vs directional leads. METHODS We conducted a retrospective analysis of ET patients with omnidirectional and directional leads implanted between 2005 and 2022. We compared patient demographics, tremor scores, and energy utilization for directional and omnidirectional leads. Contact impedance was used to normalize amplitude values between groups. Analyses were duplicated after reclassifying omnidirectional and directional based on the utilization of directional programming for 2 or more years. RESULTS A total of 24 directional leads in 22 patients and 39 omnidirectional leads in 30 patients were followed for a mean of 3.71 and 7.54 years, respectively. There was no significant difference in age or baseline tremor scores between the groups. Both lead types demonstrated increasing amplitudes over time, but directional leads had significantly less change over time, particularly in the first year (P = .0012). Patients with omnidirectional leads were more likely to experience a pulse width increase of greater than 20 µs over 1 year (41.0% vs 12.5%; P = .035). Although time to first implantable pulse generator replacement was shorter for directional leads, this was not significant (P = .062). CONCLUSION Both omnidirectional and directional deep brain stimulation reduces tremor severity in ET patients. However, directional leads offer more stable voltage requirements and less year-to-year voltage change, particularly in the first year. The increased likelihood of significant pulse width changes in omnidirectional leads suggests that directional leads may provide more sustainable therapeutic effects through other programming parameters. Ongoing research is needed to optimize deep brain stimulation technology and programming strategies to maximize patient benefit and device longevity.
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Affiliation(s)
- Tessa Harland
- Department of Neurosurgery, Albany Medical Center, Albany, New York, USA
| | - Shelby Sabourin
- Department of Experimental Therapeutics, Albany Medical Center, Albany, New York, USA
| | - Ryan Mayer
- Department of Neurosurgery, University of Arizona College of Medicine, Tucson, Arizona, USA
| | - Jennifer Durphy
- Department of Neurology, Albany Medical Center, Albany, New York, USA
| | - Octavian Adam
- Department of Neurology, Albany Medical Center, Albany, New York, USA
| | - Julie G Pilitsis
- Department of Neurosurgery, University of Arizona College of Medicine, Tucson, Arizona, USA
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Patel R, Burroughs L, Higgins A, Zauber SE, Isbaine F, Schneider D, Hohman R, Gupta K. Bilateral Deep Brain Stimulation of the Ventral Intermediate Nucleus of the Thalamus Improves Objective Acoustic Measures of Essential Vocal Tremor. Neurosurgery 2024; 95:915-923. [PMID: 38787392 DOI: 10.1227/neu.0000000000002955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2023] [Accepted: 02/28/2024] [Indexed: 05/25/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM-DBS) is an established treatment for medically refractory essential tremor. However, the effect of VIM-DBS on vocal tremor remains poorly understood, with results varying by method of vocal tremor assessment and stimulation laterality. This single-center study measures the effect of bilateral VIM-DBS on essential vocal tremor using blinded objective acoustic voice analysis. METHODS Ten patients with consecutive essential tremor with comorbid vocal tremor receiving bilateral VIM-DBS underwent voice testing before and after implantation of DBS in this prospective cohort study. Objective acoustic measures were extracted from the middle one second of steady-state phonation including cepstral peak prominence, signal-to-noise ratio, percentage voicing, tremor rate, extent of fundamental frequency modulation, and extent of intensity modulation. DBS surgery was performed awake with microelectrode recording and intraoperative testing. Postoperative voice testing was performed after stable programming. RESULTS Patients included 6 female and 4 male, with a mean age of 67 ± 6.7 years. The VIM was targeted with the following coordinates relative to the mid-anterior commissure:posterior commissure point: 13.2 ± 0.6 mm lateral, 6.2 ± 0.7 mm posterior, and 0.0 mm below. Mean programming parameters were amplitude 1.72.0 ± 0.6 mA, pulse width 63.0 ± 12.7 µs, and rate 130.6 ± 0.0 Hz. VIM-DBS significantly improved tremor rate from 4.43 ± 0.8 Hz to 3.2 ± 0.8 Hz ( P = .001) CI (0.546, 1.895), jitter from 1 ± 0.94 to 0.53 ± 0.219 ( P = .02) CI (-0.124, 1.038), cepstral peak prominence from 13.6 ± 3.9 to 18.8 ± 2.9 ( P = .016) CI (-4.100, -0.235), signal-to-noise ratio from 15.7 ± 3.9 to 18.5 ± 3.7 ( P = .02) CI (-5.598, -0.037), and articulation rate from 0.77 ± 0.2 to 0.82 ± .14 ( P = .04) CI (-0.097, 0.008). There were no major complications in this series. CONCLUSION Objective acoustic voice analyses suggest that bilateral VIM-DBS effectively reduces vocal tremor rate and improves voicing. Further studies using objective acoustic analyses and laryngeal imaging may help refine surgical and stimulation techniques and evaluate the effect of laterality on vocal tremor.
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Affiliation(s)
- Rita Patel
- Department of Otolaryngology Head & Neck Surgery, Indiana University School of Medicine, Indianapolis/Indiana University Bloomington, Bloomington , Indiana , USA
| | - Leah Burroughs
- Department of Neurosurgery, Indiana University School of Medicine, Indianapolis , Indiana , USA
| | - Alexis Higgins
- Department of Neurosurgery, Indiana University School of Medicine, Indianapolis , Indiana , USA
| | - S Elizabeth Zauber
- Department of Neurology, Indiana University School of Medicine, Indianapolis , Indiana , USA
| | - Faical Isbaine
- Department of Neurosurgery, Emory University, Atlanta , Georgia , USA
| | - Dylan Schneider
- Department of Neurosurgery, Indiana University School of Medicine, Indianapolis , Indiana , USA
| | - Ryane Hohman
- Department of Speech, Language and Hearing Sciences, Indiana University Bloomington, Bloomington , Indiana , USA
| | - Kunal Gupta
- Department of Neurosurgery, Indiana University School of Medicine, Indianapolis , Indiana , USA
- Department of Neurosurgery, Medical College of Wisconsin, Milwaukee , Wisconsin , USA
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Ghimire S, Thapa B, Neupane D, Pokharel P. Outcomes of stereotactic thalamotomy in patients of essential tremor: A systematic review. J Clin Neurosci 2024; 126:38-45. [PMID: 38824802 DOI: 10.1016/j.jocn.2024.05.036] [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: 12/25/2023] [Revised: 05/18/2024] [Accepted: 05/27/2024] [Indexed: 06/04/2024]
Abstract
BACKGROUND Essential tremor is a neurological condition associated with movement disorder with more prevalence among adult group of population. The burden of essential tremor is peaking globally but with the advancement in the area of functional neurosurgery such as stereotactic thalamotomy, the quality of life of such patients can be improved drastically. METHODS This systemic review was conducted in accordance to the guidance of preferred Reporting items for Systematic Review and Meta-Analysis(PRISMA). Databases of "PubMed", "Embase", "Web of Science", "Cinhal Plus", and "Scopus" from inception till 2023 was undertaken. A combination of keywords, Medical Subject Headings (MeSH), and search terms such as Search strategy for PubMed search was as follows: "stereotactic thalamotomy" AND "essential tremor". RESULTS This systematic review analyzed 9 studies with a total of 274 patients of essential tremor patients. Unilateral thalamotomy was carried out among 268 patients and bilateral thalamotomy in rest of the patients. Vim and Vom nucleus were the site of thalamotmy with ventral intermedius nucleus being the major one. Ten different types of clinical tremor rating scales were used to assess pre operative and post operative improvement in the tremor scales of the individual patients. Dysarthria and limb weakness was noted post operative complication in majority of the cases. CONCLUSION Our study revealed that stereotactic thalamotomy provided good functional outcome in patients of essential tremor who underwent unilateral thalamotomy compared to bilateral thalamotomy. The positive outcome outweighs the complications in such functional surgery.
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Affiliation(s)
- Sagun Ghimire
- Department of Neurosurgery, B and B Hospital, Gwarko, Lalitpur, Nepal.
| | - Bibechan Thapa
- Department of Surgery, West Hertfordshire Teaching Hospital, United Kingdom
| | - Durga Neupane
- B.P. Koirala Institute of Health Science, Dharan, Nepal
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Suresh V, Dave T, Ghosh S, Jena R, Sanker V. Deep brain stimulation in Parkinson's disease: A scientometric and bibliometric analysis, trends, and research hotspots. Medicine (Baltimore) 2024; 103:e38152. [PMID: 38758903 PMCID: PMC11098246 DOI: 10.1097/md.0000000000038152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Accepted: 04/16/2024] [Indexed: 05/19/2024] Open
Abstract
Parkinson disease (PD), a prevalent neurodegenerative ailment in the elderly, relies mainly on pharmacotherapy, yet deep brain stimulation (DBS) emerges as a vital remedy for refractory cases. This study performs a bibliometric analysis on DBS in PD, delving into research trends and study impact to offer comprehensive insights for researchers, clinicians, and policymakers, illuminating the current state and evolutionary trajectory of research in this domain. A systematic search on March 13, 2023, in the Scopus database utilized keywords like "Parkinson disease," "PD," "Parkinsonism," "Deep brain stimulation," and "DBS." The top 1000 highly cited publications on DBS in PD underwent scientometric analysis via VOS Viewer and R Studio's Bibliometrix package, covering publication characteristics, co-authorship, keyword co-occurrence, thematic clustering, and trend topics. The bibliometric analysis spanned 1984 to 2021, involving 1000 cited articles from 202 sources. The average number of citations per document were 140.9, with 31,854 references. "Movement Disorders" led in publications (n = 98), followed by "Brain" (n = 78) and "Neurology" (n = 65). The University of Oxford featured prominently. Thematic keyword clustering identified 9 core research areas, such as neuropsychological function and motor circuit electrophysiology. The shift from historical neurosurgical procedures to contemporary focuses like "beta oscillations" and "neuroethics" was evident. The bibliometric analysis emphasizes UK and US dominance, outlining 9 key research areas pivotal for reshaping Parkinson treatment. A discernible shift from invasive neurosurgery to DBS is observed. The call for personalized DBS, integration with NIBS, and exploration of innovative avenues marks the trajectory for future research.
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Affiliation(s)
- Vinay Suresh
- King George’s Medical University, Lucknow, India
| | - Tirth Dave
- Bukovinian State Medical University, Chernivtsi, Ukraine
| | | | - Rahul Jena
- Bharati Vidyapeeth Medical College, Pune, India
| | - Vivek Sanker
- Society of Brain Mapping and Therapeutics, Los Angeles, CA
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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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10
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Guehl D, Guillaud E, Langbour N, Doat E, Auzou N, Courtin E, Branchard O, Engelhardt J, Benazzouz A, Eusebio A, Cuny E, Burbaud P. Usefulness of thalamic beta activity for closed-loop therapy in essential tremor. Sci Rep 2023; 13:22332. [PMID: 38102180 PMCID: PMC10724233 DOI: 10.1038/s41598-023-49511-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 12/08/2023] [Indexed: 12/17/2023] Open
Abstract
A partial loss of effectiveness of deep brain stimulation of the ventral intermediate nucleus of the thalamus (VIM) has been reported in some patients with essential tremor (ET), possibly due to habituation to permanent stimulation. This study focused on the evolution of VIM local-field potentials (LFPs) data over time to assess the long-term feasibility of closed-loop therapy based on thalamic activity. We performed recordings of thalamic LFPs in 10 patients with severe ET using the ACTIVA™ PC + S (Medtronic plc.) allowing both recordings and stimulation in the same region. Particular attention was paid to describing the evolution of LFPs over time from 3 to 24 months after surgery when the stimulation was Off. We demonstrated a significant decrease in high-beta LFPs amplitude during movements inducing tremor in comparison to the rest condition 3 months after surgery (1.91 ± 0.89 at rest vs. 1.27 ± 1.37 µV2/Hz during posture/action for N = 8/10 patients; p = 0.010), 12 months after surgery (2.92 ± 1.75 at rest vs. 2.12 ± 1.78 µV2/Hz during posture/action for N = 7/10 patients; p = 0.014) and 24 months after surgery (2.32 ± 0.35 at rest vs 0.75 ± 0.78 µV2/Hz during posture/action for 4/6 patients; p = 0.017). Among the patients who exhibited a significant decrease of high-beta LFP amplitude when stimulation was Off, this phenomenon was observed at least twice during the follow-up. Although the extent of this decrease in high-beta LFPs amplitude during movements inducing tremor may vary over time, this thalamic biomarker of movement could potentially be usable for closed-loop therapy in the long term.
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Affiliation(s)
- Dominique Guehl
- Service de Neurophysiologie Clinique de l'enfant et de l'adulte, Hôpital Pellegrin, Pôle des Neurosciences Cliniques, CHU de Bordeaux, Bordeaux, France.
- Institut des Maladies Neurodégénératives, Univ. Bordeaux, CNRS, IMN, UMR 5293, F-33000, Bordeaux, France.
| | - Etienne Guillaud
- Institute of Cognitive and Integrative Neurosciences, Univ. Bordeaux, CNRS, INCIA, UMR 5287, F-33000, Bordeaux, France
| | - Nicolas Langbour
- Centre de Recherche en Psychiatrie, CH de la Milétrie, 86000, Poitiers, France
| | - Emilie Doat
- Institute of Cognitive and Integrative Neurosciences, Univ. Bordeaux, CNRS, INCIA, UMR 5287, F-33000, Bordeaux, France
| | - Nicolas Auzou
- Institut des Maladies Neurodégénératives Clinique (IMNc), Pôle des Neurosciences Cliniques, CHU de Bordeaux, Bordeaux, France
| | - Edouard Courtin
- Service de Neurophysiologie Clinique de l'enfant et de l'adulte, Hôpital Pellegrin, Pôle des Neurosciences Cliniques, CHU de Bordeaux, Bordeaux, France
| | | | | | - Abdelhamid Benazzouz
- Institut des Maladies Neurodégénératives, Univ. Bordeaux, CNRS, IMN, UMR 5293, F-33000, Bordeaux, France
| | - Alexandre Eusebio
- Department of Neurology and Movement Disorders, APHM, Hôpitaux Universitaire de Marseille, Marseille, France
- Institut de Neurosciences de la Timone, UMR 7289, Aix Marseille Univ, CNRS, Marseille, France
| | - Emmanuel Cuny
- Service de Neurochirurgie, CHU de Bordeaux, Bordeaux, France
| | - Pierre Burbaud
- Service de Neurophysiologie Clinique de l'enfant et de l'adulte, Hôpital Pellegrin, Pôle des Neurosciences Cliniques, CHU de Bordeaux, Bordeaux, France
- Institut des Maladies Neurodégénératives, Univ. Bordeaux, CNRS, IMN, UMR 5293, F-33000, Bordeaux, France
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11
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Stenmark Persson R, Fytagoridis A, Ryzhkov M, Hariz M, Blomstedt P. Long-Term Follow-Up of Unilateral Deep Brain Stimulation Targeting the Caudal Zona Incerta in 13 Patients with Parkinsonian Tremor. Stereotact Funct Neurosurg 2023; 101:369-379. [PMID: 37879313 DOI: 10.1159/000533793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Accepted: 08/22/2023] [Indexed: 10/27/2023]
Abstract
INTRODUCTION Deep brain stimulation (DBS) is an established treatment for Parkinson's disease (PD) and other movement disorders. The ventral intermediate nucleus of the thalamus is considered as the target of choice for tremor disorders, including tremor-dominant PD not suitable for DBS in the subthalamic nucleus (STN). In the last decade, several studies have shown promising results on tremor from DBS in the posterior subthalamic area (PSA), including the caudal zona incerta (cZi) located posteromedial to the STN. The aim of this study was to evaluate the long-term effect of unilateral cZi/PSA-DBS in patients with tremor-dominant PD. METHODS Thirteen patients with PD with medically refractory tremor were included. The patients were evaluated using the motor part of the Unified Parkinson Disease Rating Scale (UPDRS) off/on medication before surgery and off/on medication and stimulation 1-2 years (short-term) after surgery and at a minimum of 3 years after surgery (long-term). RESULTS At short-term follow-up, DBS improved contralateral tremor by 88% in the off-medication state. This improvement persisted after a mean of 62 months. Contralateral bradykinesia was improved by 40% at short-term and 20% at long-term follow-up, and the total UPDRS-III by 33% at short-term and by 22% at long-term follow-up with stimulation alone. CONCLUSIONS Unilateral cZi/PSA-DBS seems to remain an effective treatment for patients with severe Parkinsonian tremor several years after surgery. There was also a modest improvement on bradykinesia.
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Affiliation(s)
| | - Anders Fytagoridis
- Department of Clinical Neuroscience, Neurosurgery, Karolinska Institute, Stockholm, Sweden
| | - Maxim Ryzhkov
- Cranial and Spinal Technologies, Medtronic, Lafayette, Colorado, USA
| | - Marwan Hariz
- Department of Clinical Science, Neurosciences, Umeå University, Umeå, Sweden
- UCL Queen Square Institute of Neurology, London, UK
| | - Patric Blomstedt
- Department of Clinical Science, Neurosciences, Umeå University, Umeå, Sweden
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12
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Kondapavulur S, Silva AB, Molinaro AM, Wang DD. A Systematic Review Comparing Focused Ultrasound Surgery With Radiosurgery for Essential Tremor. Neurosurgery 2023; 93:524-538. [PMID: 37010324 PMCID: PMC10553193 DOI: 10.1227/neu.0000000000002462] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2022] [Accepted: 01/26/2023] [Indexed: 04/04/2023] Open
Abstract
BACKGROUND Focused ultrasound (FUS-T) and stereotactic radiosurgery thalamotomy (SRS-T) targeting the ventral intermediate nucleus are effective incisionless surgeries for essential tremor (ET). However, their efficacy for tremor reduction and, importantly, adverse event incidence have not been directly compared. OBJECTIVE To present a comprehensive systematic review with network meta-analysis examining both efficacy and adverse events (AEs) of FUS-T vs SRS-T for treating medically refractory ET. METHODS We conducted a systematic review and network meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using the PubMed and Embase databases. We included all primary FUS-T/SRS-T studies with approximately 1-year follow-up, with unilateral Fahn-Tolosa-Marin Tremor Rating Scale or Clinical Rating Scale for Tremor scores prethalamotomy/post-thalamotomy and/or AEs. The primary efficacy outcome was Fahn-Tolosa-Marin Tremor Rating Scale A+B score reduction. AEs were reported as an estimated incidence. RESULTS Fifteen studies of 464 patients and 3 studies of 62 patients met inclusion criteria for FUS-T/SRS-T efficacy comparison, respectively. Network meta-analysis demonstrated similar tremor reduction between modalities (absolute tremor reduction: FUS-T: -11.6 (95% CI: -13.3, -9.9); SRS-T: -10.3 (95% CI: -14.2, -6.0). FUS-T had a greater 1-year adverse event rate, particularly imbalance and gait disturbances (10.5%) and sensory disturbances (8.3%). Contralateral hemiparesis (2.7%) often accompanied by speech impairment (2.4%) were most common after SRS-T. There was no correlation between efficacy and lesion volume. CONCLUSION Our systematic review found similar efficacy between FUS-T and SRS-T for ET, with trend toward higher efficacy yet greater adverse event incidence with FUS-T. Smaller lesion volumes could mitigate FUS-T off-target effects for greater safety.
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Affiliation(s)
- Sravani Kondapavulur
- Department of Neurological Surgery, UCSF, San Francisco, California, USA
- Medical Scientist Training Program, UCSF, San Francisco, California, USA
| | - Alexander B. Silva
- Department of Neurological Surgery, UCSF, San Francisco, California, USA
- Medical Scientist Training Program, UCSF, San Francisco, California, USA
| | | | - Doris D. Wang
- Department of Neurological Surgery, UCSF, San Francisco, California, USA
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13
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Olivier C, Lamy JC, Kosutzka Z, Van Hamme A, Cherif S, Lau B, Vidailhet M, Karachi C, Welter ML. Cerebellar Transcranial Alternating Current Stimulation in Essential Tremor Patients with Thalamic Stimulation: A Proof-of-Concept Study. Neurotherapeutics 2023; 20:1109-1119. [PMID: 37097344 PMCID: PMC10457262 DOI: 10.1007/s13311-023-01372-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/19/2023] [Indexed: 04/26/2023] Open
Abstract
Essential tremor (ET) is a disabling condition resulting from a dysfunction of cerebello-thalamo-cortical circuitry. Deep brain stimulation (DBS) or lesion of the ventral-intermediate thalamic nucleus (VIM) is an effective treatment for severe ET. Transcranial cerebellar brain stimulation has recently emerged as a non-invasive potential therapeutic option. Here, we aim to investigate the effects of high-frequency non-invasive cerebellar transcranial alternating current stimulation (tACS) in severe ET patients already operated for VIM-DBS. Eleven ET patients with VIM-DBS, and 10 ET patients without VIM-DBS and matched for tremor severity, were included in this double-blind proof-of-concept controlled study. All patients received unilateral cerebellar sham-tACS and active-tACS for 10 min. Tremor severity was blindly assessed at baseline, without VIM-DBS, during sham-tACS, during and at 0, 20, 40 min after active-tACS, using kinetic recordings during holding posture and action ('nose-to-target') task and videorecorded Fahn-Tolosa-Marin (FTM) clinical scales. In the VIM-DBS group, active-tACS significantly improved both postural and action tremor amplitude and clinical (FTM scales) severity, relative to baseline, whereas sham-tACS did not, with a predominant effect for the ipsilateral arm. Tremor amplitude and clinical severity were also not significantly different between ON VIM-DBS and active-tACS conditions. In the non-VIM-DBS group, we also observed significant improvements in ipsilateral action tremor amplitude, and clinical severity after cerebellar active-tACS, with a trend for improved postural tremor amplitude. In non-VIM-DBS group, sham- active-tACS also decreased clinical scores. These data support the safety and potential efficacy of high-frequency cerebellar-tACS to reduce ET amplitude and severity.
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Affiliation(s)
- Claire Olivier
- Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, 47 Bd de L'Hôpital, 75013, Paris, France
- PANAM Core Facility, Institut du Cerveau - Paris Brain Institute, Paris, France
| | - Jean-Charles Lamy
- Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, 47 Bd de L'Hôpital, 75013, Paris, France
- PANAM Core Facility, Institut du Cerveau - Paris Brain Institute, Paris, France
- Department of Neurology, AP-HP, Hôpital Salpetriere, DMU Neuroscience 6, Paris, France
| | - Zuzana Kosutzka
- Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, 47 Bd de L'Hôpital, 75013, Paris, France
- Department of Neurology, AP-HP, Hôpital Salpetriere, DMU Neuroscience 6, Paris, France
| | - Angèle Van Hamme
- Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, 47 Bd de L'Hôpital, 75013, Paris, France
- PANAM Core Facility, Institut du Cerveau - Paris Brain Institute, Paris, France
| | - Saoussen Cherif
- Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, 47 Bd de L'Hôpital, 75013, Paris, France
| | - Brian Lau
- Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, 47 Bd de L'Hôpital, 75013, Paris, France
| | - Marie Vidailhet
- Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, 47 Bd de L'Hôpital, 75013, Paris, France
- Department of Neurology, AP-HP, Hôpital Salpetriere, DMU Neuroscience 6, Paris, France
| | - Carine Karachi
- Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, 47 Bd de L'Hôpital, 75013, Paris, France
- Department of Neurosurgery, AP-HP, Hôpital Salpetriere, Paris, France
| | - Marie-Laure Welter
- Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Sorbonne Université, 47 Bd de L'Hôpital, 75013, Paris, France.
- PANAM Core Facility, Institut du Cerveau - Paris Brain Institute, Paris, France.
- Clinical Investigation Center, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, Paris, France.
- Department of Neurophysiology, Rouen University Hospital, University of Rouen, Rouen, France.
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14
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Ferreira Felloni Borges Y, Cheyuo C, Lozano AM, Fasano A. Essential Tremor - Deep Brain Stimulation vs. Focused Ultrasound. Expert Rev Neurother 2023; 23:603-619. [PMID: 37288812 DOI: 10.1080/14737175.2023.2221789] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 06/01/2023] [Indexed: 06/09/2023]
Abstract
INTRODUCTION Essential Tremor (ET) is one of the most common tremor syndromes typically presented as action tremor, affecting mainly the upper limbs. In at least 30-50% of patients, tremor interferes with quality of life, does not respond to first-line therapies and/or intolerable adverse effects may occur. Therefore, surgery may be considered. AREAS COVERED In this review, the authors discuss and compare unilateral ventral intermedius nucleus deep brain stimulation (VIM DBS) and bilateral DBS with Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thalamotomy, which comprises focused acoustic energy generating ablation under real-time MRI guidance. Discussion includes their impact on tremor reduction and their potential complications. Finally, the authors provide their expert opinion. EXPERT OPINION DBS is adjustable, potentially reversible and allows bilateral treatments; however, it is invasive requires hardware implantation, and has higher surgical risks. Instead, MRgFUS is less invasive, less expensive, and requires no hardware maintenance. Beyond these technical differences, the decision should also involve the patient, family, and caregivers.
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Affiliation(s)
- Yuri Ferreira Felloni Borges
- Edmond J. Safra Program in Parkinson's Disease, Division of Neurology, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, University of Toronto, Toronto, ON, Canada
| | - Cletus Cheyuo
- Division of Neurosurgery, Toronto Western Hospital, University Health Network, Toronto, ON, Canada
| | - Andres M Lozano
- Division of Neurosurgery, Toronto Western Hospital, University Health Network, Toronto, ON, Canada
- Krembil Brain Institute, Toronto, ON, Canada
| | - Alfonso Fasano
- Edmond J. Safra Program in Parkinson's Disease, Division of Neurology, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, University of Toronto, Toronto, ON, Canada
- Krembil Brain Institute, Toronto, ON, Canada
- Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, ON, Canada
- Department of Parkinson's Disease & Movement Disorders Rehabilitation, Moriggia-Pelascini Hospital, Gravedona Ed Uniti, Como, Italy
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15
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Zea Vera A, Gropman AL. Surgical treatment of movement disorders in neurometabolic conditions. Front Neurol 2023; 14:1205339. [PMID: 37333007 PMCID: PMC10272416 DOI: 10.3389/fneur.2023.1205339] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 05/16/2023] [Indexed: 06/20/2023] Open
Abstract
Refractory movement disorders are a common feature of inborn errors of metabolism (IEMs), significantly impacting quality of life and potentially leading to life-threatening complications such as status dystonicus. Surgical techniques, including deep brain stimulation (DBS) and lesioning techniques, represent an additional treatment option. However, the application and benefits of these procedures in neurometabolic conditions is not well understood. This results in challenges selecting surgical candidates and counseling patients preoperatively. In this review, we explore the literature of surgical techniques for the treatment of movement disorders in IEMs. Globus pallidus internus DBS has emerged as a beneficial treatment option for dystonia in Panthotate-Kinase-associated Neurodegeneration. Additionally, several patients with Lesch-Nyhan Disease have shown improvement following pallidal stimulation, with more robust effects on self-injurious behavior than dystonia. Although there are numerous reports describing benefits of DBS for movement disorders in other IEMs, the sample sizes have generally been small, limiting meaningful conclusions. Currently, DBS is preferred to lesioning techniques. However, successful use of pallidotomy and thalamotomy in neurometabolic conditions has been reported and may have a role in selected patients. Surgical techniques have also been used successfully in patients with IEMs to treat status dystonicus. Advancing our knowledge of these treatment options could significantly improve the care for patients with neurometabolic conditions.
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Affiliation(s)
- Alonso Zea Vera
- Division of Neurology, Children’s National Hospital, Washington, DC, United States
- Department of Neurology, George Washington University School of Medicine and Health Sciences, Washington, DC, United States
| | - Andrea L. Gropman
- Department of Neurology, George Washington University School of Medicine and Health Sciences, Washington, DC, United States
- Division of Neurogenetics and Neurodevelopmental Pediatrics, Children’s National Hospital, Washington DC, United States
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16
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Aleid A, Aleid M, Alehaiwi G, Alharbi H, Alhuthayli A, Al Rebih ZM, Alhumaidi N, Albashrawi W, Bazarah RS, Alharbi A, Alhejji AH, Aldawood HA, AlHumud O, Alkathem JA, Almalki S. Advancements in the Clinical Outcomes of Functional Neurosurgery With Deep Brain Stimulation for Movement Disorders: A Literature Review. Cureus 2023; 15:e40350. [PMID: 37456406 PMCID: PMC10339274 DOI: 10.7759/cureus.40350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/13/2023] [Indexed: 07/18/2023] Open
Abstract
This literature review explores recent advancements in deep brain stimulation (DBS) surgery for movement disorders. It highlights notable improvements, including closed-loop stimulation techniques, optogenetics, and improved surgical targeting. Positive clinical outcomes with low complication rates and improved motor symptoms are consistently reported. The review emphasizes the importance of minimizing risks through meticulous surgical practices and discusses potential complications associated with DBS surgery. Future prospects focus on enhancing technology, refining surgical techniques, and conducting further research. Closed-loop stimulation optimizes DBS efficacy by tailoring stimulation parameters to individual patient needs. Optogenetics offers precise modulation of neural activity with light-sensitive proteins, enabling more targeted treatments. Cybersecurity measures are essential due to the integration of wireless and digital technologies in DBS systems. DBS surgery has significantly improved the management of movement disorders with its safety and effectiveness. Ongoing research in closed-loop stimulation, optogenetics, and cybersecurity is expected to further enhance DBS technology and outcomes, benefiting patients with treatment-resistant movement disorders.
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Affiliation(s)
- Abdulsalam Aleid
- Department of Neurosurgery, King Faisal University, Al Ahsa, SAU
| | - Masowma Aleid
- Department of Neurosurgery, Medical College, King Faisal University, Al Ahsa, SAU
| | - Ghadeer Alehaiwi
- Department of Biological Sciences, Umm-Al Qura University, Mecca, SAU
| | - Hajar Alharbi
- Department of Pediatric Surgery, Gdańsk Medical University, Gdańsk, POL
| | - Abdulaziz Alhuthayli
- Department of Pharmaceutical Care, General Network for Healthcare Providers Hospital, Kharj, SAU
| | - Zainb M Al Rebih
- Department of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, SAU
- Department of Surgery, Imam Abdulrahman Bin Faisal University, Dammam, SAU
| | | | - Wihad Albashrawi
- Department of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, SAU
- Department of Surgery, Imam Abdulrahman Bin Faisal University, Dammam, SAU
| | | | - Anas Alharbi
- College of Medicine, Imam Muhammad Ibn Saud Islamic University (IMSIU), Riyadh, SAU
| | - Ahmed H Alhejji
- Department of Surgery, College of Veterinary Medicine, Al Ahsa, SAU
| | - Hassan A Aldawood
- Neurosurgery, College of Medicine, Imam Abdurrahman Bin Faisal University, Dammam, SAU
| | - Osama AlHumud
- Department of Medicine, King Faisal University, Al Ahsa, SAU
- Department of Surgery, King Faisal University, Al Ahsa, SAU
| | - Jafar A Alkathem
- Department of Internal Medicine, King Faisal University, Al Ahsa, SAU
| | - Sami Almalki
- Department of Neurosurgery, King Faisal University, Al Ahsa, SAU
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17
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Pourahmad R, Saleki K, Esmaili M, Abdollahi A, Alijanizadeh P, Gholinejad MZ, Banazadeh M, Ahmadi M. Deep brain stimulation (DBS) as a therapeutic approach in gait disorders: What does it bring to the table? IBRO Neurosci Rep 2023; 14:507-513. [PMID: 37304345 PMCID: PMC10248795 DOI: 10.1016/j.ibneur.2023.05.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2023] [Revised: 05/17/2023] [Accepted: 05/18/2023] [Indexed: 06/13/2023] Open
Abstract
Gait deficits are found in various degenerative central nervous system conditions, and are particularly a hallmark of Parkinson's disease (PD). While there is no cure for such neurodegenerative disorders, Levodopa is considered as the standard medication in PD patients. Often times, the therapy of severe PD consists of deep brain stimulation (DBS) of the subthalamic nucleus. Earlier research exploring the effect of gait have reported contradictory results or insufficient efficacy. A change in gait includes various parameters, such as step length, cadence, Double-stance phase duration which may be positively affected by DBS. DBS could also be effective in correcting the levodopa-induced postural sway abnormalities. Moreover, during normal walking, interaction among the subthalamic nucleus and cortex -essential regions which exert a role in locomotion- are coupled. However, during the freezing of gait, the activity is desynchronized. The mechanisms underlying DBS-induced neurobehavioral improvements in such scenarios requires further study. The present review discusses DBS in the context of gait, the benefits associated with DBS compared to standard pharmacotherapy options, and provides insights into future research.
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Affiliation(s)
- Ramtin Pourahmad
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Tehran, Iran
| | - Kiarash Saleki
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
- Department of e-Learning, Virtual School of Medical Education and Management, Shahid Beheshti University of Medical Sciences(SBMU), Tehran, Iran
- USERN Office, Babol University of Medical Sciences, Babol, Iran
| | | | - Arian Abdollahi
- School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Parsa Alijanizadeh
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
- USERN Office, Babol University of Medical Sciences, Babol, Iran
| | | | - Mohammad Banazadeh
- Pharmaceutical Sciences and Cosmetic Products Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Mona Ahmadi
- Department of Neurology, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
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18
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Blomstedt Y, Stenmark Persson R, Awad A, Hariz G, Philipson J, Hariz M, Fytagoridis A, Blomstedt P. 10 Years Follow-Up of Deep Brain Stimulation in the Caudal Zona Incerta/Posterior Subthalamic Area for Essential Tremor. Mov Disord Clin Pract 2023; 10:783-793. [PMID: 37205250 PMCID: PMC10187013 DOI: 10.1002/mdc3.13729] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 01/18/2023] [Accepted: 03/03/2023] [Indexed: 10/27/2023] Open
Abstract
BACKGROUND Long-term data on the effects of deep brain stimulation (DBS) for essential tremor (ET) is scarce, especially regarding DBS in the caudal Zona incerta (cZi) and the posterior subthalamic area (PSA). OBJECTIVES The aim of this prospective study was to evaluate the effect of cZi/PSA DBS in ET at 10 years after surgery. METHODS Thirty-four patients were included. All patients received cZi/PSA DBS (5 bilateral/29 unilateral) and were evaluated at regular intervals using the essential tremor rating scale (ETRS). RESULTS One year after surgery, there was a 66.4% improvement of total ETRS and 70.7% improvement of tremor (items 1-9) compared with the preoperative baseline. Ten years after surgery, 14 patients had died and 3 were lost to follow-up. In the remaining 17 patients, a significant improvement was maintained (50.8% for total ETRS and 55.8% for tremor items). On the treated side the scores of hand function (items 11-14) had improved by 82.6% at 1 year after surgery, and by 66.1% after 10 years. Since off-stimulation scores did not differ between year 1 and 10, this 20% deterioration of on-DBS scores was interpreted as a habituation. There was no significant increase in stimulation parameters beyond the first year. CONCLUSIONS This 10 year follow up study, found cZi/PSA DBS for ET to be a safe procedure with a mostly retained effect on tremor, compared to 1 year after surgery, and in the absence of increase in stimulation parameters. The modest deterioration of effect of DBS on tremor was interpreted as habituation.
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Affiliation(s)
- Yulia Blomstedt
- Department of Public Health and Clinical MedicineUmeå UniversityUmeåSweden
- Department of Clinical Science, NeuroscienceUmeå UniversityUmeåSweden
| | | | - Amar Awad
- Department of Clinical Science, NeuroscienceUmeå UniversityUmeåSweden
- Department of Integrative Medical Biology, Physiology SectionUmeå UniversityUmeåSweden
| | - Gun‐Marie Hariz
- Department of Clinical Science, NeuroscienceUmeå UniversityUmeåSweden
| | - Johanna Philipson
- Department of Clinical Science, NeuroscienceUmeå UniversityUmeåSweden
| | - Marwan Hariz
- Department of Clinical Science, NeuroscienceUmeå UniversityUmeåSweden
- UCL Institute of Neurology, Queen SquareLondonUK
| | | | - Patric Blomstedt
- Department of Clinical Science, NeuroscienceUmeå UniversityUmeåSweden
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19
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Abstract
Parkinson's disease (PD) is a progressive neurodegenerative illness with both motor and nonmotor symptoms. Deep brain stimulation (DBS) is an established safe neurosurgical symptomatic therapy for eligible patients with advanced disease in whom medical treatment fails to provide adequate symptom control and good quality of life, or in whom dopaminergic medications induce severe side effects such as dyskinesias. DBS can be tailored to the patient's symptoms and targeted to various nodes along the basal ganglia-thalamus circuitry, which mediates the various symptoms of the illness; DBS in the thalamus is most efficient for tremors, and DBS in the pallidum most efficient for rigidity and dyskinesias, whereas DBS in the subthalamic nucleus (STN) can treat both tremors, akinesia, rigidity and dyskinesias, and allows for decrease in doses of medications even in patients with advanced stages of the disease, which makes it the preferred target for DBS. However, DBS in the STN assumes that the patient is not too old, with no cognitive decline or relevant depression, and does not exhibit severe and medically resistant axial symptoms such as balance and gait disturbances, and falls. Dysarthria is the most common side effect of DBS, regardless of the brain target. DBS has a long-lasting effect on appendicular symptoms, but with progression of disease, nondopaminergic axial features become less responsive to DBS. DBS for PD is highly specialised; to enable adequate selection and follow-up of patients, DBS requires dedicated multidisciplinary teams of movement disorder neurologists, functional neurosurgeons, specialised DBS nurses and neuropsychologists.
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Affiliation(s)
- Marwan Hariz
- Department of Clinical Neuroscience, University Hospital of Umeå, Umeå, Sweden.,UCL-Queen Square Institute of Neurology, London, UK
| | - Patric Blomstedt
- Department of Clinical Neuroscience, University Hospital of Umeå, Umeå, Sweden
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20
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Techniques of Frameless Robot-Assisted Deep Brain Stimulation and Accuracy Compared with the Frame-Based Technique. Brain Sci 2022; 12:brainsci12070906. [PMID: 35884713 PMCID: PMC9313029 DOI: 10.3390/brainsci12070906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Revised: 06/30/2022] [Accepted: 07/07/2022] [Indexed: 11/30/2022] Open
Abstract
Background: Frameless robot-assisted deep brain stimulation (DBS) is an innovative technique for leads implantation. This study aimed to evaluate the accuracy and precision of this technique using the Sinovation SR1 robot. Methods: 35 patients with Parkinson’s disease who accepted conventional frame-based DBS surgery (n = 18) and frameless robot-assisted DBS surgery (n = 17) by the same group of neurosurgeons were analyzed. The coordinate of the tip of the intended trajectory was recorded as xi, yi, and zi. The actual position of lead implantation was recorded as xa, ya, and za. The vector error was calculated by the formula of √(xi − xa)2 + (yi − ya)2 + (zi − za)2 to evaluate the accuracy. Results: The vector error was 1.52 ± 0.53 mm (range: 0.20–2.39 mm) in the robot-assisted group and was 1.77 ± 0.67 mm (0.59–2.98 mm) in the frame-based group with no significant difference between two groups (p = 0.1301). In 10.7% (n = 3) frameless robot-assisted implanted leads, the vector error was greater than 2.00 mm with a maximum offset of 2.39 mm, and in 35.5% (n = 11) frame-based implanted leads, the vector error was larger than 2.00 mm with a maximum offset of 2.98 mm. Leads were more posterior than planned trajectories in the robot-assisted group and more medial and posterior in the conventional frame-based group. Conclusions: Awake frameless robot-assisted DBS surgery was comparable to the conventional frame-based technique in the accuracy and precision for leads implantation.
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21
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Österlund E, Blomstedt P, Fytagoridis A. Ipsilateral Effects of Unilateral Deep Brain Stimulation for Essential Tremor. Stereotact Funct Neurosurg 2022; 100:248-252. [PMID: 35760039 DOI: 10.1159/000525325] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 05/06/2022] [Indexed: 11/19/2022]
Abstract
BACKGROUND Essential tremor (ET) is the most common adult movement disorder. For the relatively large group of patients who do not respond adequately to pharmacological therapy, deep brain stimulation (DBS) is a well-established treatment option. Most ET patients will have bilateral symptoms, and many of them receive bilateral DBS. Unilateral DBS is however still the most common procedure, and some papers suggest an ipsilateral effect in these patients. OBJECTIVES The aim of this study was to analyze if there is an ipsilateral effect of DBS for ET. METHOD We retrospectively analyzed our patient cohort with DBS surgery from 1996 to 2017, selecting patients with ET that underwent surgery with unilateral DBS without previous DBS or lesional surgery. A total number of 68 patients (39 males, 29 females) were identified. The patients were evaluated twice: first, at a mean time of 12 months after surgery defined as short-term follow-up and then again at a mean time of 49 months after surgery defined as long-term follow-up, using the clinical rating scale for tremor (CRST). RESULTS The total CRST score was reduced from mean 49.5 points at baseline before surgery to 20.2 (p < 0.001) at short-term and 28.3 (p < 0.001) at long-term follow-up. Contralateral tremor was reduced from mean 6.1 to 0.4 (p < 0.001) and 1.2 (p < 0.001), respectively. Contralateral hand function was reduced from 11.5 to 2.6 (p < 0.001) and 4.6 (p < 0.001), respectively. Ipsilateral hand function scored 9 at baseline, 8.3 at 1 year, and then again 9.4 at long-term follow-up. Ipsilateral tremor scored 4.0 at baseline, 3.7 at 1 year, and 4.3 at long-term follow-up. Neither ipsilateral hand function nor ipsilateral tremor showed significant difference. CONCLUSIONS There was no difference in severity of ipsilateral tremor, neither at 1 year nor in the long term. We believe ipsilateral effects of DBS for ET merits limited consideration regarding decision-making or patient counseling before surgery.
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Affiliation(s)
- Erik Österlund
- Department of Clinical Neuroscience, Neurosurgery, Karolinska Institutet, Solna, Sweden
| | - Patric Blomstedt
- Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå, Sweden
| | - Anders Fytagoridis
- Department of Clinical Neuroscience, Neurosurgery, Karolinska Institutet, Solna, Sweden
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22
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Prakash P, Deuschl G, Ozinga S, Mitchell KT, Cheeran B, Larson PS, Merola A, Groppa S, Tomlinson T, Ostrem JL. Benefits and Risks of a Staged‐Bilateral VIM versus Unilateral VIM DBS for Essential Tremor. Mov Disord Clin Pract 2022; 9:775-784. [PMID: 35937489 PMCID: PMC9346253 DOI: 10.1002/mdc3.13490] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 04/23/2022] [Accepted: 05/11/2022] [Indexed: 11/16/2022] Open
Abstract
Background Despite over 30 years of clinical experience, high‐quality studies on the efficacy of bilateral versus unilateral deep brain stimulation (DBS) of the ventral intermediate (VIM) nucleus of the thalamus for medically refractory essential tremor (ET) remain limited. Objectives To compare benefits and risks of bilateral versus unilateral VIM DBS using the largest ET DBS clinical trial dataset available to date. Methods Participants from the US St. Jude/Abbott pivotal ET DBS trial who underwent staged‐bilateral VIM implantation constituted the primary cohort in this sub‐analysis. Their assessments “on” DBS at six months after second‐side VIM DBS implantation were compared to the assessments six months after unilateral implantation. Two control cohorts of participants with unilateral implantation only were also used for between‐group comparisons. Results The primary cohort consisted of n = 38 ET patients (22M/16F; age of 65.3 ± 9.5 years). The second side VIM‐DBS resulted in a 29.6% additional improvement in the total motor CRST score (P < 0.001), with a 64.1% CRST improvement in the contralateral side (P < 0.001). An added improvement was observed in the axial tremor score (21.4%, P = 0.005), and CRST part B (24.8%, P < 0.001) score. Rate of adverse events was slightly higher after bilateral stimulation. Conclusions In the largest ET DBS study to date, staged‐bilateral VIM DBS was a highly effective treatment for ET with bilateral implantation resulting in greater reduction in total motor tremor scores when compared to unilateral stimulation alone.
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Affiliation(s)
- Prarthana Prakash
- Department of Neurology, UCSF Weill Institute for Neurosciences, Movement Disorder and Neuromodulation Center University of California San Francisco CA United States
| | - Guenther Deuschl
- Department of Neurology, Universitatsklinikum Schleswig‐Holstein, Kiel Campus Christian Albrechts University Kiel Kiel Germany
| | - Sarah Ozinga
- Abbott, Clinical Research Department 6901 Preston Road Plano TX 75024 USA
| | | | - Binith Cheeran
- Abbott, Clinical Research Department 6901 Preston Road Plano TX 75024 USA
| | - Paul S. Larson
- Department of Neurosurgery University of Arizona Tuscon AZ
| | - Aristide Merola
- Department of Neurology, Madden Center for Parkinson Disease and other Movement Disorders Ohio State University Wexner Medical Center Columbus OH United States
| | - Sergiu Groppa
- Department of Neurology, Focus Program Translational Neuroscience University Medical Center of the Johannes Gutenberg‐University Mainz Mainz Germany
| | - Tucker Tomlinson
- Abbott, Clinical Research Department 6901 Preston Road Plano TX 75024 USA
| | - Jill L. Ostrem
- Department of Neurology, UCSF Weill Institute for Neurosciences, Movement Disorder and Neuromodulation Center University of California San Francisco CA United States
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23
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Amerika WE, van der Gaag S, Mosch A, van der Gaag NA, Hoffmann CF, Zutt R, Marinus J, Contarino MF. Medical and surgical treatment for medication‐induced tremor: case report and systematic review. Mov Disord Clin Pract 2022; 9:676-687. [PMID: 35844282 PMCID: PMC9274355 DOI: 10.1002/mdc3.13463] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Revised: 01/30/2022] [Accepted: 04/05/2022] [Indexed: 11/11/2022] Open
Affiliation(s)
- Wardell E. Amerika
- Department of Neurology Haga Teaching Hospital The Hague The Netherlands
| | | | - Arne Mosch
- Department of Neurology Haga Teaching Hospital The Hague The Netherlands
| | | | | | - Rodi Zutt
- Department of Neurology Haga Teaching Hospital The Hague The Netherlands
| | - Johan Marinus
- Department of Neurology Leiden University Medical Center Leiden the Netherlands
| | - Maria Fiorella Contarino
- Department of Neurology Haga Teaching Hospital The Hague The Netherlands
- Department of Neurology Leiden University Medical Center Leiden the Netherlands
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24
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Kondapavulur S, Silva AB, Wang DD. Ventral Intermediate Nucleus of the Thalamus versus Posterior Subthalamic Area: Network Meta-Analysis of DBS Target Site Efficacy for Essential Tremor. Stereotact Funct Neurosurg 2022; 100:224-235. [PMID: 35350022 DOI: 10.1159/000522573] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Accepted: 02/03/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND Deep brain stimulation (DBS) targeting the ventral intermediate nucleus (Vim) of the thalamus or the posterior subthalamic area (PSA) are effective treatments for essential tremor (ET). However, their relative efficacy is unknown. OBJECTIVE Here, we present the first systematic review and network meta-analysis, examining the efficacy of Vim versus PSA DBS for treating medically refractory ET. METHODS We included all primary studies that reported validated Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) scores pre-/postimplantation or on-/off-stimulation postimplantation, for patients receiving either Vim or PSA DBS. The primary outcome was FTM-TRS score reduction; the secondary outcome was percent reduction in score. We categorized all outcomes as short-term (≤12 months) or long-term (>12 months). RESULTS For pre-/postimplantation comparisons, 19 and 11 studies met inclusion criteria for short- and long-term follow-ups, respectively. For on-/off-stimulation tremor score comparisons, 8 studies met inclusion criteria for short-term follow-up. Network meta-analysis of pre-/postimplantation tremor scores showed greater tremor reduction with PSA implantation short-term (absolute tremor reduction: PSA: -30.94 [95% confidence interval (CI): -34.93, -26.95]; Vim: -26.26 [95% CI: -33.39, -19.12]; relative tremor reduction: PSA: 63.3% [95% CI: 61.8%-64.8%]; Vim: 57.8% [95% CI: 56.5%-59.0%]). However, there was no difference in efficacy between PSA and Vim DBS when comparing tremor on-versus off-stimulation at short-term follow-up or pre- versus postimplantation tremor reduction long-term. CONCLUSION Our systematic review highlighted both heterogeneity in scoring systems used and lack of transparency in reporting total scores, limiting direct comparison across studies. We found a modestly superior efficacy with PSA stimulation in the short term, but no difference in tremor reduction long-term.
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Affiliation(s)
- Sravani Kondapavulur
- Department of Neurological Surgery, UCSF, San Francisco, California, USA.,Medical Scientist Training Program, UCSF, San Francisco, California, USA
| | - Alexander B Silva
- Department of Neurological Surgery, UCSF, San Francisco, California, USA.,Medical Scientist Training Program, UCSF, San Francisco, California, USA
| | - Doris D Wang
- Department of Neurological Surgery, UCSF, San Francisco, California, USA
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25
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Abstract
Deep-brain stimulation (DBS) is an emerging research topic aiming to improve the quality of life of patients with brain diseases, and a great deal of effort has been focused on the development of implantable devices. This paper presents a low-noise amplifier (LNA) for the acquisition of biopotentials on DBS. This electronic module was designed in a low-voltage/low-power CMOS process, targeting implantable applications. The measurement results showed a gain of 38.6 dB and a −3 dB bandwidth of 2.3 kHz. The measurements also showed a power consumption of 2.8 μW. Simulations showed an input-referred noise of 6.2 μVRMS. The LNA occupies a microdevice area of 122 μm × 283 μm, supporting its application in implanted systems.
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26
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Shetty N. Essential Tremor-Do We Have Better Therapeutics? A Review of Recent Advances and Future Directions. Curr Neurol Neurosci Rep 2022; 22:197-208. [PMID: 35235170 DOI: 10.1007/s11910-022-01185-8] [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] [Accepted: 01/18/2022] [Indexed: 11/30/2022]
Abstract
PURPOSE OF REVIEW Essential tremor (ET) is a very common condition that significantly impacts quality of life. Current medical treatments are quite limited, and while surgical treatments like deep brain stimulation (DBS) can be very effective, they come with their own limitations as well as procedural risks. This article reviews updates on recent advances and future directions in the treatment of ET. RECENT FINDINGS A new generation of pharmacologic agents specifically designed for ET is in clinical trials. Advances in DBS technology continue to improve this therapy. MRI-guided focused ultrasound (MRgFUS) is now an approved noninvasive ablative treatment for ET that is effective and shows potential for continuing improvement. The first peripheral stimulation device for ET has also now been approved. This article reviews updates on the treatment of ET, encompassing pharmacologic agents in clinical trials, DBS, MRgFUS, and noninvasive stimulation therapies. Recent treatment advances and future directions of development show a great deal of promise for ET therapeutics.
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Affiliation(s)
- Neil Shetty
- Parkinson's Disease and Movement Disorders Center, Department of Neurology, Northwestern University Feinberg School of Medicine, Abbott Hall, 11th Floor, 710 N. Lake Shore Drive, Chicago, IL, 60611, USA.
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27
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Bai Y, Yin Z, Diao Y, Hu T, Yang A, Meng F, Zhang J. Loss of long-term benefit from VIM-DBS in essential tremor: A secondary analysis of repeated measurements. CNS Neurosci Ther 2021; 28:279-288. [PMID: 34866345 PMCID: PMC8739044 DOI: 10.1111/cns.13770] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 10/18/2021] [Accepted: 11/16/2021] [Indexed: 11/26/2022] Open
Abstract
AIMS Deep brain stimulation (DBS) in the ventral intermediate nucleus (Vim-DBS) is the preferred surgical therapy for essential tremor (ET). Tolerance and disease progression are considered to be the two main reasons underlying the loss of long-term efficacy of Vim-DBS. This study aimed to explore whether Vim-DBS shows long-term loss of efficacy and to evaluate the reasons for this diminished efficacy from different aspects. METHODS In a repeated-measures meta-analysis of 533 patients from 18 studies, Vim-DBS efficacy was evaluated at ≤6 months, 7-12 months, 1-3 years, and ≥4 years. The primary outcomes were the score changes in different components of the Fahn-Tolosa-Marin Tremor Rating Scale (TRS; total score, motor score, hand-function score, and activities of daily living [ADL] score). Secondary outcomes were the long-term predictive factors. RESULTS The TRS total, motor, and ADL scores showed significant deterioration with disease progression (p = 0.002, p = 0.047, and p < 0.001, respectively), while the TRS total (p < 0.001), hand-function (p = 0.036), and ADL (p = 0.004) scores indicated a significant long-term reduction in DBS efficacy, although the motor subscore indicated no loss of efficacy. Hand-function (p < 0.001) and ADL (p = 0.028) scores indicated DBS tolerance, while the TRS total and motor scores did not. Stimulation frequency and preoperative score were predictive factors for long-term results. CONCLUSION This study provides level 3a evidence that long-term Vim-DBS is effective in controlling motor symptoms without waning benefits. The efficacy reduction for hand function was caused by DBS tolerance, while that for ADL was caused by DBS tolerance and disease progression. More attention should be given to actual functional recovery rather than changes in motor scores in patients with ET.
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Affiliation(s)
- Yutong Bai
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Neurostimulation, Beijing, China
| | - Zixiao Yin
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Neurostimulation, Beijing, China
| | - Yu Diao
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Neurostimulation, Beijing, China
| | - Tianqi Hu
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Neurostimulation, Beijing, China
| | - Anchao Yang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Neurostimulation, Beijing, China
| | - Fangang Meng
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Neurostimulation, Beijing, China
| | - Jianguo Zhang
- Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,Beijing Key Laboratory of Neurostimulation, Beijing, China
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28
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Abstract
Essential tremor (ET) is one of the most common movement disorders, with a reported >60 million affected individuals worldwide. The definition and underlying pathophysiology of ET are contentious. Patients present primarily with motor features such as postural and action tremors, but may also have other non-motor features, including cognitive impairment and neuropsychiatric symptoms. Genetics account for most of the ET risk but environmental factors may also be involved. However, the variable penetrance and challenges in validating data make gene-environment analysis difficult. Structural changes in cerebellar Purkinje cells and neighbouring neuronal populations have been observed in post-mortem studies, and other studies have found GABAergic dysfunction and dysregulation of the cerebellar-thalamic-cortical circuitry. Commonly prescribed medications include propranolol and primidone. Deep brain stimulation and ultrasound thalamotomy are surgical options in patients with medically intractable ET. Further research in post-mortem studies, and animal and cell-based models may help identify new pathophysiological clues and therapeutic targets and, together with advances in omics and machine learning, may facilitate the development of precision medicine for patients with ET.
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29
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Peters J, Tisch S. Habituation After Deep Brain Stimulation in Tremor Syndromes: Prevalence, Risk Factors and Long-Term Outcomes. Front Neurol 2021; 12:696950. [PMID: 34413826 PMCID: PMC8368435 DOI: 10.3389/fneur.2021.696950] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Accepted: 07/02/2021] [Indexed: 12/12/2022] Open
Abstract
Deep brain stimulation (DBS) of the thalamus is an effective treatment for medically refractory essential, dystonic and Parkinson's tremor. It may also provide benefit in less common tremor syndromes including, post-traumatic, cerebellar, Holmes, neuropathic and orthostatic tremor. The long-term benefit of DBS in essential and dystonic tremor (ET/DT) often wanes over time, a phenomena referred to as stimulation "tolerance" or "habituation". While habituation is generally accepted to exist, it remains controversial. Attempts to quantify habituation have revealed conflicting reports. Placebo effects, loss of micro-lesional effect, disease related progression, suboptimal stimulation and stimulation related side-effects may all contribute to the loss of sustained long-term therapeutic effect. Habituation often presents as substantial loss of initial DBS benefit occurring as early as a few months after initial stimulation; a complex and feared issue when faced in the setting of optimal electrode placement. Simply increasing stimulation current tends only to propagate tremor severity and induce stimulation related side effects. The report by Paschen and colleagues of worsening tremor scores in the "On" vs. "Off" stimulation state over time, even after accounting for "rebound" tremor, supports the concept of habituation. However, these findings have not been consistent across all studies. Chronic high intensity stimulation has been hypothesized to induce detrimental plastic effects on tremor networks, with some lines of evidence that DT and ET may be more susceptible than Parkinson's tremor to habituation. However, Tsuboi and colleague's recent longitudinal follow-up in dystonic and "pure" essential tremor suggests otherwise. Alternatively, post-mortem findings support a biological adaption to stimulation. The prevalence and etiology of habituation is still not fully understood and management remains difficult. A recent study reported that alternating thalamic stimulation parameters at weekly intervals provided improved stability of tremor control consistent with reduced habituation. In this article the available evidence for habituation after DBS for tremor syndromes is reviewed; including its prevalence, time-course, possible mechanisms; along with expected long-term outcomes for tremor and factors that may assist in predicting, preventing and managing habituation.
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Affiliation(s)
- James Peters
- Department of Neurology, St Vincent's Hospital, Sydney, NSW, Australia
| | - Stephen Tisch
- Department of Neurology, St Vincent's Hospital, Sydney, NSW, Australia
- School of Medicine, University of New South Wales, Sydney, NSW, Australia
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30
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Ma Z, Wei L, Du X, Hou S, Chen F, Jiao Q, Liu A, Liu S, Wang J, Shen H. Two-photon calcium imaging of neuronal and astrocytic responses: the influence of electrical stimulus parameters and calcium signaling mechanisms. J Neural Eng 2021; 18. [PMID: 34130271 DOI: 10.1088/1741-2552/ac0b50] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2021] [Accepted: 06/15/2021] [Indexed: 12/30/2022]
Abstract
Objective. Electrical brain stimulation has been used to ameliorate symptoms associated with neurologic and psychiatric disorders. The astrocytic activation and its interaction with neurons may contribute to the therapeutic effects of electrical stimulation. However, how the astrocytic activity is affected by electrical stimulation and its calcium signaling mechanisms remain largely unknown. This study is to explore the influence of electrical stimulus parameters on cellular calcium responses and corresponding calcium signaling mechanisms, with a focus on the heretofore largely overlooked astrocytes.Approach. Usingin vivotwo-photon microscopy in mouse somatosensory cortex, the calcium activity in neurons and astrocytes were recorded.Main results. The cathodal stimulation evoked larger responses in both neurons and astrocytes than anodal stimulation. Both neuronal and astrocytic response profiles exhibited the unimodal frequency dependency, the astrocytes prefer higher frequency stimulation than neurons. Astrocytes need longer pulse width and higher current intensity than neurons to activate. Compared to neurons, the astrocytes were not capable of keeping sustained calcium elevation during prolonged electrical stimulation. The neuronal Ca2+influx involves postsynaptic effects and direct depolarization. The Ca2+surge of astrocytes has a neuronal origin, the noradrenergic and glutamatergic signaling act synergistically to induce astrocytic activity.Significance. The astrocytic activity can be regulated by manipulating stimulus parameters and its calcium activation should be fully considered when interpreting the mechanisms of action of electrical neuromodulation. This study brings considerable benefits in the application of electrical stimulation and provides useful insights into cortical signal transduction, which contributes to the understanding of mechanisms underlying the therapeutic efficacy of electrical stimulation for neurorehabilitation applications.
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Affiliation(s)
- Zengguang Ma
- School of Biomedical Engineering, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China
| | - Liangpeng Wei
- School of Biomedical Engineering, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China
| | - Xiaolang Du
- Department of Pharmacy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Shaowei Hou
- School of Biomedical Engineering, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China
| | - Feng Chen
- School of Biomedical Engineering, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China
| | - Qingyan Jiao
- School of Biomedical Engineering, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China
| | - Aili Liu
- School of Biomedical Engineering, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China
| | - Shujing Liu
- School of Biomedical Engineering, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China
| | - Junsong Wang
- School of Biomedical Engineering, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China
| | - Hui Shen
- School of Biomedical Engineering, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China.,Research Institute of Neurology, General Hospital, Tianjin Medical University, Tianjin 300052, China
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31
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Rammo RA, Ozinga SJ, White A, Nagel SJ, Machado AG, Pallavaram S, Cheeran BJ, Walter BL. Directional Stimulation in Parkinson's Disease and Essential Tremor: The Cleveland Clinic Experience. Neuromodulation 2021; 25:829-835. [PMID: 33733515 DOI: 10.1111/ner.13374] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 01/18/2021] [Accepted: 02/01/2021] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To assess use of directional stimulation in Parkinson's disease and essential tremor patients programmed in routine clinical care. MATERIALS AND METHODS Patients with Parkinson's disease or essential tremor implanted at Cleveland Clinic with a directional deep brain stimulation (DBS) system from November 2017 to October 2019 were included in this retrospective case series. Omnidirectional was compared against directional stimulation using therapeutic current strength, therapeutic window percentage, and total electrical energy delivered as outcome variables. RESULTS Fifty-seven Parkinson's disease patients (36 males) were implanted in the subthalamic nucleus (105 leads) and 33 essential tremor patients (19 males) were implanted in the ventral intermediate nucleus of the thalamus (52 leads). Seventy-four percent of patients with subthalamic stimulation (65% of leads) and 79% of patients with thalamic stimulation (79% of leads) were programmed with directional stimulation for their stable settings. Forty-six percent of subthalamic leads and 69% of thalamic leads were programmed on single segment activation. There was no correlation between the length of microelectrode trajectory through the STN and use of directional stimulation. CONCLUSIONS Directional programming was more common than omnidirectional programming. Substantial gains in therapeutic current strength, therapeutic window, and total electrical energy were found in subthalamic and thalamic leads programmed on directional stimulation.
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Affiliation(s)
- Richard A Rammo
- Center For Neurological Restoration, Cleveland Clinic, Cleveland, OH, USA
| | | | - Alexandra White
- Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Sean J Nagel
- Center For Neurological Restoration, Cleveland Clinic, Cleveland, OH, USA
| | - Andre G Machado
- Center For Neurological Restoration, Cleveland Clinic, Cleveland, OH, USA
| | | | | | - Benjamin L Walter
- Center For Neurological Restoration, Cleveland Clinic, Cleveland, OH, USA
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Dissociative Tremor Response with Pallidal Deep Brain Stimulation in Parkinson's Disease. Tremor Other Hyperkinet Mov (N Y) 2020; 10:53. [PMID: 33362947 PMCID: PMC7747761 DOI: 10.5334/tohm.568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Background: Pallidal and subthalamic targets are commonly used for deep brain stimulation in Parkinson’s disease (PD), with similar efficacy for resting tremor control. However, neuromodulatory effects on kinetic and postural tremor in PD is less clear. Case Report: We present a 67-year-old PD patient with marked dissociative tremor response following pallidal neuromodulation. We observed excellent resting tremor suppression, but postural and kinetic tremors remained severe, requiring additional thalamic VIM stimulation for management. Discussion: Our findings illustrate the phenotypical differences in PD and differential response to diverse tremor characteristics with distinctive stimulation targets. Additional studies are necessary to understand these differences.
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Giordano M, Caccavella VM, Zaed I, Foglia Manzillo L, Montano N, Olivi A, Polli FM. Comparison between deep brain stimulation and magnetic resonance-guided focused ultrasound in the treatment of essential tremor: a systematic review and pooled analysis of functional outcomes. J Neurol Neurosurg Psychiatry 2020; 91:1270-1278. [PMID: 33055140 DOI: 10.1136/jnnp-2020-323216] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Revised: 08/22/2020] [Accepted: 09/09/2020] [Indexed: 01/01/2023]
Abstract
The current gold standard surgical treatment for medication-resistant essential tremor (ET) is deep brain stimulation (DBS). However, recent advances in technologies have led to the development of incisionless techniques, such as magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy. The authors perform a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to compare unilateral MRgFUS thalamotomy to unilateral and bilateral DBS in the treatment of ET in terms of tremor severity and quality of life improvement. PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials and SCOPUS databases were searched. 45 eligible articles, published between 1990 and 2019, were retrieved. 1202 patients were treated with DBS and 477 were treated with MRgFUS thalamotomy. Postoperative tremor improvement was greater following DBS than MRgFUS thalamotomy (p<0.001). A subgroup analysis was carried out stratifying by treatment laterality: bilateral DBS was significantly superior to both MRgFUS and unilateral DBS (p<0.001), but no significant difference was recorded between MRgFUS and unilateral DBS (p<0.198). Postoperative quality of life improvement was significantly greater following MRgFUS thalamotomy than DBS (p<0.001). Complications were differently distributed among the two groups (p<0.001). Persistent complications were significantly more common in the MRgFUS group (p=0.042). While bilateral DBS proves superior to unilateral MRgFUS thalamotomy in the treatment of ET, a subgroup analysis suggests that treatment laterality is the most significant determinant of tremor improvement, thus highlighting the importance of future investigations on bilateral staged MRgFUS thalamotomy.
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Affiliation(s)
- Martina Giordano
- Department of Neurosurgery, University Hospital Agostino Gemelli, Roma, Italy
| | | | - Ismail Zaed
- Department of Neurosurgery, Humanitas Clinical and Research Center, Rozzano, Italy
| | | | - Nicola Montano
- Department of Neurosurgery, University Hospital Agostino Gemelli, Roma, Italy
| | - Alessandro Olivi
- Department of Neurosurgery, University Hospital Agostino Gemelli, Roma, Italy
| | - Filippo Maria Polli
- Department of Neurosurgery, University Hospital Agostino Gemelli, Roma, Italy
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Cong F, Liu X, Liu CSJ, Xu X, Shen Y, Wang B, Zhuo Y, Yan L. Improved depiction of subthalamic nucleus and globus pallidus internus with optimized high-resolution quantitative susceptibility mapping at 7 T. NMR IN BIOMEDICINE 2020; 33:e4382. [PMID: 32686241 DOI: 10.1002/nbm.4382] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 07/03/2020] [Accepted: 07/06/2020] [Indexed: 06/11/2023]
Abstract
The subthalamic nucleus (STN) and globus pallidus internus (GPi) are commonly used targets in deep-brain stimulation (DBS) surgery for the treatment of movement disorders. The success of DBS critically depends on the spatial precision of stimulation. By taking advantage of good contrast between iron-rich deep-brain nuclei and surrounding tissues, quantitative susceptibility mapping (QSM) has shown promise in differentiating the STN and GPi from the adjacent substantia nigra and globus pallidus externus, respectively. Nonlinear morphology-enabled dipole inversion (NMEDI) is a widely used QSM algorithm, but the image quality of reconstructed susceptibility maps relies on the regularization parameter selection. To date, few studies have systematically optimized the regularization parameter at the ultra-high field of 7 T. In this study, we optimized the regularization parameter in NMEDI to improve the depiction of STN and GPi at different spatial resolutions at both 3 T and 7 T. The optimized QSM images were further compared with other susceptibility-based images, including T2*-weighted (T2*w), R2*, susceptibility-weighted, and phase images. QSM showed better depiction of deep-brain nuclei with clearer boundaries compared with the other methods, and 7 T QSM at 0.35 × 0.35 × 1.0 mm3 demonstrated superior performance to the others. Our findings suggest that optimized high-resolution QSM at 7 T allows for improved delineation of deep-brain nuclei with clear and sharp borders between nuclei, which may become a promising tool for DBS nucleus preoperative localization.
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Affiliation(s)
- Fei Cong
- State Key Laboratory of Brain and Cognitive Science, Beijing MRI Center for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Xueru Liu
- State Key Laboratory of Brain and Cognitive Science, Beijing MRI Center for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Chia-Shang Jason Liu
- Department of Radiology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Xin Xu
- Department of Neurosurgery, General Hospital of PLA, Beijing, China
| | - Yelong Shen
- Shandong Provincial Hospital affiliated to Shandong First Medical University, Shandong, China
| | - Bo Wang
- State Key Laboratory of Brain and Cognitive Science, Beijing MRI Center for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Yan Zhuo
- State Key Laboratory of Brain and Cognitive Science, Beijing MRI Center for Brain Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Lirong Yan
- Stevens Neuroimaging and Informatics Institute, Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
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35
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Wang KL, Ren Q, Chiu S, Patel B, Meng FG, Hu W, Shukla AW. Deep brain stimulation and other surgical modalities for the management of essential tremor. Expert Rev Med Devices 2020; 17:817-833. [PMID: 33081571 DOI: 10.1080/17434440.2020.1806709] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
INTRODUCTION Surgical treatments are considered for essential tremor (ET) when patients do not respond to oral pharmacological therapies. These treatments mainly comprise radiofrequency (RF) thalamotomy, gamma knife radiosurgery (GKRS), deep brain stimulation (DBS), and focused ultrasound (FUS) procedures. AREAS COVERED We reviewed the strengths and weaknesses of each procedure and clinical outcomes for 7 RF studies (n = 85), 11 GKRS (n = 477), 33 DBS (n = 1061), and 13 FUS studies (n = 368). A formal comparison was not possible given the heterogeneity in studies. Improvements were about 42%-90% RF, 10%-79% GKRS, 45%-83% DBS, 42%-83% FUS at short-term follow-up (<12 months) and were about 54%-82% RF, 11%-84% GKRS, 18%-92% DBS, and 42%-80% FUS at long-term follow-up (>12 months). EXPERT OPINION We found DBS with inherent advantages of being an adjustable and reversible procedure as the most frequently employed surgical procedure for control of ET symptoms. FUS is a promising procedure but has limited applicability for unilateral control of symptoms. RF is invasive, and GKRS has unpredictable delayed effects. Each of these surgical modalities has advantages and limitations that need consideration when selecting a treatment for the ET patients.
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Affiliation(s)
- Kai-Liang Wang
- Department of Neurosurgery, Xuanwu Hospital, Capital Medical University , Beijing, China.,Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University , Beijing, China
| | - Qianwei Ren
- Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University , Beijing, China
| | - Shannon Chiu
- Department of Neurology, University of Florida College of Medicine , Gainesville, FL, USA
| | - Bhavana Patel
- Department of Neurology, University of Florida College of Medicine , Gainesville, FL, USA
| | - Fan-Gang Meng
- Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University , Beijing, China
| | - Wei Hu
- Department of Neurology, University of Florida College of Medicine , Gainesville, FL, USA
| | - Aparna Wagle Shukla
- Department of Neurology, University of Florida College of Medicine , Gainesville, FL, USA
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36
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Ruckart KW, Moya-Mendez ME, Nagatsuka M, Barry JL, Siddiqui MS, Madden LL. Comprehensive Evaluation of Voice-Specific Outcomes in Patients With Essential Tremor Before and After Deep Brain Stimulation. J Voice 2020; 36:838-846. [PMID: 33071149 DOI: 10.1016/j.jvoice.2020.09.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 09/11/2020] [Accepted: 09/14/2020] [Indexed: 10/23/2022]
Abstract
OBJECTIVE Deep brain stimulation (DBS) is a treatment for medically refractory essential tremor (ET), but there is a paucity of literature examining the effects of DBS on voice in patients with ET pre-DBS and post-DBS. This study aimed to report a comprehensive evaluation of voice in patients with ET pre-DBS and 6-months post-DBS. STUDY DESIGN Case series. METHODS Five patients receiving DBS for ET underwent voice evaluations pre-DBS and 6-months post-DBS. One patient had concurrent ET of the vocal tract (ETVT). The evaluation included patient-reported, perceptual, acoustic, and phonatory aerodynamic analyses of voice. Voice Handicap Index-10, Grade, Roughness, Breathiness, Asthenia, Strain Scale, perturbation measures, cepstral spectral index of dysphonia, cepstral peak prominence, and mean phonatory airflow measures were also among the data collected. RESULTS Patients with ET presented with minimal changes in perceptual, acoustic, and phonatory aerodynamic parameters. Perceived vocal roughness significantly increased 6-months post-DBS (P = 0.047). The patient with ETVT presented with clinically significant improvement in almost all collected voice parameters 6-months post-DBS. CONCLUSION This is the first study to provide data encompassing auditory perceptual voice analysis, voice-specific patient-reported quality of life measures, acoustic, and phonatory aerodynamic outcomes in patients pre-DBS and 6-months post-DBS for ET. The results of our preliminary study have implications for the use of a comprehensive voice assessment to identify and measure change in voice outcomes in patients with ET and ETVT pre- and postsurgery.
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Affiliation(s)
- Kathryn W Ruckart
- Department of Otolaryngology Head and Neck Surgery, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina.
| | | | - Moeko Nagatsuka
- Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Julia L Barry
- Department of Otolaryngology Head and Neck Surgery, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina
| | - Mustafa S Siddiqui
- Department of Neurology, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina
| | - Lyndsay L Madden
- Department of Otolaryngology Head and Neck Surgery, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina
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Reitz SC, Luger S, Lapa S, Eibach M, Filmann N, Seifert V, Weise L, Klein JC, Kang JS, Baudrexel S, Quick-Weller J. Comparing Programming Sessions of Vim-DBS. Front Neurol 2020; 11:987. [PMID: 33013651 PMCID: PMC7494809 DOI: 10.3389/fneur.2020.00987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 07/28/2020] [Indexed: 11/13/2022] Open
Abstract
Background: Essential Tremor (ET) is a progressive neurological disorder characterized by postural and kinetic tremor most commonly affecting the hands and arms. Medically intractable ET can be treated by deep brain stimulation (DBS) of the ventral intermediate nucleus of thalamus (VIM). We investigated whether the location of the effective contact (most tremor suppression with at least side effects) in VIM-DBS for ET changes over time, indicating a distinct mechanism of loss of efficacy that goes beyond progression of tremor severity, or a mere reduction of DBS efficacy. Methods: We performed programming sessions in 10 patients who underwent bilateral vim-DBS surgery between 2009 and 2017 at our department. In addition to the intraoperative (T1) and first clinical programming session (T2) a third programming session (T3) was performed to assess the effect- and side effect threshold (minimum voltage at which a tremor suppression or side effects occurred). Additionally, we compared the choice of the effective contact between T1 and T2 which might be affected by a surgical induced “brain shift.” Discussion: Over a time span of about 4 years VIM-DBS in ET showed continuous efficacy in tremor suppression during stim-ON compared to stim-OFF. Compared to immediate postoperative programming sessions in ET-patients with DBS, long-term evaluation showed no relevant change in the choice of contact with respect to side effects and efficacy. In the majority of the cases the active contact at T2 did not correspond to the most effective intraoperative stimulation site T1, which might be explained by a brain-shift due to cerebral spinal fluid loss after neurosurgical procedure.
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Affiliation(s)
- Sarah C Reitz
- Department of Neurology, University Hospital, Frankfurt, Germany
| | - Sebastian Luger
- Department of Neurology, University Hospital, Frankfurt, Germany
| | - Sriramya Lapa
- Department of Neurology, University Hospital, Frankfurt, Germany
| | - Michael Eibach
- Department of Neurosurgery, University Hospital, Frankfurt, Germany
| | - Natalie Filmann
- Division of Neurosurgery, Dalhouse University Halifax, Halifax, NS, Canada.,Institute of Biostatistics and Mathematical Modeling, University Hospital, Goethe University, Frankfurt, Germany
| | - Volker Seifert
- Department of Neurosurgery, University Hospital, Frankfurt, Germany
| | - Lutz Weise
- Division of Neurosurgery, Dalhouse University Halifax, Halifax, NS, Canada
| | - Johannes C Klein
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom
| | - Jun-Suk Kang
- Department of Neurology, University Hospital, Frankfurt, Germany
| | - Simon Baudrexel
- Department of Neurology, University Hospital, Frankfurt, Germany
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38
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Ågren R, Bartek J, Johansson A, Blomstedt P, Fytagoridis A. Pulse Width and Implantable Pulse Generator Longevity in Pallidal Deep Brain Stimulation for Dystonia: A Population-Based Comparative Effectiveness Study. Stereotact Funct Neurosurg 2020; 98:331-336. [PMID: 32668433 DOI: 10.1159/000508794] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Accepted: 05/18/2020] [Indexed: 11/19/2022]
Abstract
INTRODUCTION A wide range of pulse widths (PWs) has been used in globus pallidus internus (GPi) deep brain stimulation (DBS) for dystonia. However, no specific PW has demonstrated clinical superiority, and the paradigm may differ among DBS centers. OBJECTIVE To investigate how different paradigms of PWs in GPi DBS for dystonia affect implantable pulse generator (IPG) longevities and energy consumption. METHODS Thirty-nine patients with dystonia treated with bilateral GPi DBS at 2 Swedish DBS centers from 2005 to 2015 were included. Different PW paradigms were used at the 2 centers, 60-90 µs (short PWs) and 450 µs (long PW), respectively. The frequency of IPG replacements, pulse effective voltage (PEV), IPG model, pre-/postoperative imaging, and clinical outcome based on the clinical global impression (CGI) scale were collected from the medical charts and compared between the 2 groups. RESULTS The average IPG longevity was extended for the short PWs (1,129 ± 50 days) compared to the long PW (925 ± 32 days; χ2 = 12.31, p = 0.0005, log-rank test). IPG longevity correlated inversely with PEV (Pearson's r = -0.667, p < 0.0001). IPG longevities did not differ between Kinetra® and Activa® PC in the short (p = 0.319) or long PW group (p = 0.858). Electrode distances to the central sensorimotor region of the GPi did not differ between the short or long PW groups (p = 0.595). Pre- and postoperative CGI did not differ between groups. CONCLUSIONS Short PWs were associated with decreased energy consumption and increased IPG longevity. These effects were not dependent on the IPG model or the anatomic location of the electrodes. PWs did not correlate with symptom severities or clinical outcomes. The results suggest that the use of short PWs might be more energy efficient and could therefore be preferred initially when programming patients with GPi DBS for dystonia.
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Affiliation(s)
- Richard Ågren
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden,
| | - Jiri Bartek
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.,Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden.,Department of Medicine, Karolinska Institutet, Stockholm, Sweden.,Department of Neurosurgery, Rigshospitalet, Copenhagen, Sweden
| | - Anders Johansson
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Patric Blomstedt
- Department of Pharmacology and Clinical Neuroscience, Unit of Functional and Stereotactic Neurosurgery, Umeå University, Umeå, Sweden
| | - Anders Fytagoridis
- Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.,Department of Neurosurgery, Karolinska University Hospital, Stockholm, Sweden
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Wang S, Wang X, Zhao M, Li T, Zhang C, Wang M, Luan G, Guan Y. Long-term efficacy and cognitive effects of voltage-based deep brain stimulation for drug-resistant essential tremor. Clin Neurol Neurosurg 2020; 194:105940. [PMID: 32480294 DOI: 10.1016/j.clineuro.2020.105940] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2020] [Revised: 05/16/2020] [Accepted: 05/17/2020] [Indexed: 02/08/2023]
Abstract
OBJECTIVES To analyze the long-term efficacy and cognitive effects of voltage-based deep brain stimulation (DBS) for drug-resistant essential tremor (ET). PATIENTS AND METHODS Patients with drug-resistant ET and treated by voltage-based DBS of the ventral intermediate nucleus (VIM-DBS) were continuously enrolled. Seizure outcomes were assessed by blinded observers using the Tremor Rating Scale (TRS). The full-scale intelligence quotient, full-scale memory quotient, Hamilton Depression Scale, Hamilton Anxiety Scale, and Quality of Life in Essential Tremor Questionnaire were assessed as measures of cognitive function. RESULTS Eleven patients met the inclusion criteria, and two of them were excluded because of loss to follow-up. The patient follow-up times ranged from 48 to 66 months (median 51 months). TRS scores decreased by 60.4% and 46.0% at the 12- and 48-month follow-ups, respectively. Both changes were highly significant. During the follow-up period, the patients' intelligence and memory had not significantly changed; depression, anxiety, and quality of life significantly improved. After long-term follow-up, the stimulation efficacy and quality of life gradually decreased, and the depression and anxiety levels increased. CONCLUSION For patients with drug-resistant ET, voltage-based DBS can provide acceptable benefits on tremor, cognitive function, and quality of life. However, the efficacy of VIM-DBS decreased over time.
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Affiliation(s)
- Shu Wang
- Department of Neurosurgery, SanBo Brain Hospital, Capital Medical University, Beijing 100093, China.
| | - Xiongfei Wang
- Department of Neurosurgery, SanBo Brain Hospital, Capital Medical University, Beijing 100093, China
| | - Meng Zhao
- Department of Neurosurgery, SanBo Brain Hospital, Capital Medical University, Beijing 100093, China
| | - Tianfu Li
- Department of Neurology, SanBo Brain Hospital, Capital Medical University, Beijing 100093, China; Beijing Key Laboratory of Epilepsy, Beijing 100093, China; Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing 100093, China
| | - Chunsheng Zhang
- Department of Neurosurgery, SanBo Brain Hospital, Capital Medical University, Beijing 100093, China
| | - Mengyang Wang
- Department of Neurology, SanBo Brain Hospital, Capital Medical University, Beijing 100093, China
| | - Guoming Luan
- Department of Neurosurgery, SanBo Brain Hospital, Capital Medical University, Beijing 100093, China; Beijing Key Laboratory of Epilepsy, Beijing 100093, China; Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing 100093, China
| | - Yuguang Guan
- Department of Neurosurgery, SanBo Brain Hospital, Capital Medical University, Beijing 100093, China; Beijing Key Laboratory of Epilepsy, Beijing 100093, China; Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing 100093, China.
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40
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Deng H, Yue JK, Wang DD. Trends in safety and cost of deep brain stimulation for treatment of movement disorders in the United States: 2002-2014. Br J Neurosurg 2020; 35:57-64. [PMID: 32476485 DOI: 10.1080/02688697.2020.1759776] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
PURPOSE Deep brain stimulation (DBS) is being increasingly utilized to treat movement disorders including Parkinson's disease (PD), essential tremor (ET), and dystonia. An improved understanding of national trends in safety and cost is necessary. Herein, our objectives are to (1) characterize complication, mortality, and cost profiles of patients undergoing DBS for movement disorders in the United States, (2) identify predictors of morbidity and mortality, and (3) evaluate impact of complications on cost. METHODS DBS surgeries were extracted from the National Inpatient Sample (NIS) 2002-2014 for the clinical indications of PD, ET, and dystonia. Patient characteristics and eight complication categories (hardware malfunction, infection, neurological, other haemorrhagic, thromboembolic, cardiac, pulmonary, and renal/urinary) were reviewed. Outcomes included complications, mortality, hospitalization length, and inflation-adjusted cost. RESULTS There were 44,866 weighted admissions (PD-73.5%, ET-22.7%, dystonia-3.8%). The number of procedures increased 2.22-fold from 2002 to 2014 (N = 2372 in 2002; N = 5260 in 2014). Inpatient cost was $22,802 ± 13,164, remaining stable from 2002 to 2014 ($24,188 ± 15,910, $20,630 ± 11,031, respectively). Four percent experienced complications (dystonia-6.0%, PD-4.4%, ET-3.1%, p < .001). In-hospital mortality was 0.2%. Cost was greater in patients with complications ($36,306 ± 29,263 vs. $22,196 ± 11,560, p < .001). Most common complications were renal/urinary (1.5%), neurological (1.1%), and pulmonary (0.7%). Thromboembolic, pulmonary, and haemorrhagic complications were associated with greatest cost. CONCLUSION Increased DBS utilization for adult movement disorders in the United States from 2002 to 2014 was attributed to rapid adoption by teaching hospitals for PD. DBS remains a safe procedure with low overall complications and stable inpatient costs from 2002 to 2014. Complication risks vary by type of movement disorder, and although rare, multiple complications increase morbidity and cost of care.
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Affiliation(s)
- Hansen Deng
- Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
| | - John K Yue
- Department of Neurological Surgery, University of California, San Francisco, CA, USA
| | - Doris D Wang
- Department of Neurological Surgery, University of California, San Francisco, CA, USA
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41
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Diaz A, Cajigas I, Cordeiro JG, Mahavadi A, Sur S, Di Luca DG, Shpiner DS, Luca CC, Jagid JR. Individualized Anatomy-Based Targeting for VIM-cZI DBS in Essential Tremor. World Neurosurg 2020; 140:e225-e233. [PMID: 32438003 DOI: 10.1016/j.wneu.2020.04.240] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 04/29/2020] [Accepted: 04/30/2020] [Indexed: 01/30/2023]
Abstract
BACKGROUND Deep brain stimulation of the ventral intermediate nucleus (VIM) or caudal zona incerta (cZI) is effective for refractory essential tremor (ET). To refine stereotactic planning for lead placement, we developed a unique individualized anatomy-based planning protocol that targets both the VIM and the cZI in patients with ET. METHODS 33 patients with ET underwent VIM-cZI lead implantation with targeting based on our protocol. Indirect targeting was adjusted based on anatomic landmarks as reference lines bisecting the red nuclei and ipsilateral subthalamus. Outcomes were evaluated through the follow-up of 31.1 ± 18.4 months. Active contact coordinates were obtained from reconstructed electrodes in the Montreal Neurological Institute space using the MATLAB Lead-DBS toolbox. RESULTS Mean tremor improvement was 79.7% ± 22.4% and remained stable throughout the follow-up period. Active contacts at last postoperative visit had mean Montreal Neurological Institute coordinates of 15.5 ± 1.6 mm lateral to the intercommissural line, 15.3 ± 1.8 mm posterior to the anterior commissure, and 1.4 ± 2.9 mm below the intercommissural plane. No hemorrhagic complications were observed in the analyzed group. CONCLUSIONS Individualized anatomy-based VIM-cZI targeting is feasible and safe and is associated with favorable tremor outcomes.
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Affiliation(s)
- Anthony Diaz
- Department of Neurological Surgery, University of Miami, Miami, Florida, USA
| | - Iahn Cajigas
- Department of Neurological Surgery, University of Miami, Miami, Florida, USA
| | - Joacir G Cordeiro
- Department of Neurological Surgery, University of Miami, Miami, Florida, USA
| | - Anil Mahavadi
- Department of Neurological Surgery, University of Miami, Miami, Florida, USA
| | - Samir Sur
- Department of Neurological Surgery, University of Miami, Miami, Florida, USA
| | | | | | - Corneliu C Luca
- Department of Neurology, University of Miami, Miami, Florida, USA
| | - Jonathan R Jagid
- Department of Neurological Surgery, University of Miami, Miami, Florida, USA.
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42
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Eleopra R, Rinaldo S, Devigili G, Mondani M, D’Auria S, Lettieri C, Ius T, Skrap M. Frameless Deep Brain Stimulation Surgery: A Single-Center Experience and Retrospective Analysis of Placement Accuracy of 220 Electrodes in a Series of 110 Patients. Stereotact Funct Neurosurg 2020; 97:337-346. [DOI: 10.1159/000503335] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Accepted: 09/13/2019] [Indexed: 11/19/2022]
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43
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Islam R, Cuellar CA, Felmlee B, Riccelli T, Silvernail J, Boschen SL, Grahn P, Lavrov I. Multifactorial motor behavior assessment for real-time evaluation of emerging therapeutics to treat neurologic impairments. Sci Rep 2019; 9:16503. [PMID: 31712725 PMCID: PMC6848091 DOI: 10.1038/s41598-019-52806-1] [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: 07/02/2019] [Accepted: 10/15/2019] [Indexed: 12/31/2022] Open
Abstract
Integrating multiple assessment parameters of motor behavior is critical for understanding neural activity dynamics during motor control in both intact and dysfunctional nervous systems. Here, we described a novel approach (termed Multifactorial Behavioral Assessment (MfBA)) to integrate, in real-time, electrophysiological and biomechanical properties of rodent spinal sensorimotor network activity with behavioral aspects of motor task performance. Specifically, the MfBA simultaneously records limb kinematics, multi-directional forces and electrophysiological metrics, such as high-fidelity chronic intramuscular electromyography synchronized in time to spinal stimulation in order to characterize spinal cord functional motor evoked potentials (fMEPs). Additionally, we designed the MfBA to incorporate a body weight support system to allow bipedal and quadrupedal stepping on a treadmill and in an open field environment to assess function in rodent models of neurologic disorders that impact motor activity. This novel approach was validated using, a neurologically intact cohort, a cohort with unilateral Parkinsonian motor deficits due to midbrain lesioning, and a cohort with complete hind limb paralysis due to T8 spinal cord transection. In the SCI cohort, lumbosacral epidural electrical stimulation (EES) was applied, with and without administration of the serotonergic agonist Quipazine, to enable hind limb motor functions following paralysis. The results presented herein demonstrate the MfBA is capable of integrating multiple metrics of motor activity in order to characterize relationships between EES inputs that modulate mono- and polysynaptic outputs from spinal circuitry which in turn, can be used to elucidate underlying electrophysiologic mechanisms of motor behavior. These results also demonstrate that proposed MfBA is an effective tool to integrate biomechanical and electrophysiology metrics, synchronized to therapeutic inputs such as EES or pharmacology, during body weight supported treadmill or open field motor activities, to target a high range of variations in motor behavior as a result of neurological deficit at the different levels of CNS.
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Affiliation(s)
- Riazul Islam
- Department of Neurology, Mayo Clinic, Rochester, MN, USA
| | - Carlos A Cuellar
- Centro de Investigación en Ciencias de la Salud (CICSA), Universidad Anáhuac México, Campus Norte, Huixquilucan, State of Mexico, Mexico
| | - Ben Felmlee
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA
| | | | | | | | - Peter Grahn
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA
- Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA
| | - Igor Lavrov
- Department of Neurology, Mayo Clinic, Rochester, MN, USA.
- Department of Neurologic Surgery, Mayo Clinic, Rochester, MN, USA.
- Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
- Department of Biomedical Engineering, Mayo Clinic, Rochester, MN, USA.
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44
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Abstract
The mechanisms of appetite disorders, such as refractory obesity and anorexia nervosa, have been vigorously studied over the last century, and these studies have shown that the central nervous system has significant involvement with, and responsibility for, the pathology associated with these diseases. Because deep brain stimulation has been shown to be a safe, efficacious, and adjustable treatment modality for a variety of other neurological disorders, it has also been studied as a possible treatment for appetite disorders. In studies of refractory obesity in animal models, the ventromedial hypothalamus, the lateral hypothalamus, and the nucleus accumbens have all demonstrated elements of success as deep brain stimulation targets. Multiple targets for deep brain stimulation have been proposed for anorexia nervosa, with research predominantly focusing on the subcallosal cingulate, the nucleus accumbens, and the stria terminalis and medial forebrain bundle. Human deep brain stimulation studies that focus specifically on refractory obesity and anorexia nervosa have been performed but with limited numbers of patients. In these studies, the target for refractory obesity has been the lateral hypothalamus, ventromedial hypothalamus, and nucleus accumbens, and the target for anorexia nervosa has been the subcallosal cingulate. These studies have shown promising findings, but further research is needed to elucidate the long-term efficacy of deep brain stimulation for the treatment of appetite disorders.
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Affiliation(s)
- Alexander C Whiting
- 1Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and
| | - Michael Y Oh
- 2Department of Neurosurgery, Allegheny Health Network, Pittsburgh, Pennsylvania
| | - Donald M Whiting
- 2Department of Neurosurgery, Allegheny Health Network, Pittsburgh, Pennsylvania
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45
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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: 4] [Impact Index Per Article: 0.7] [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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46
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Sharma S, Pandey S. Treatment of essential tremor: current status. Postgrad Med J 2019; 96:84-93. [DOI: 10.1136/postgradmedj-2019-136647] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Revised: 08/14/2019] [Accepted: 09/13/2019] [Indexed: 12/18/2022]
Abstract
Essential tremor is the most common cause of tremor involving upper limbs, head and voice. The first line of treatment for limb tremor is pharmacotherapy with propranolol or primidone. However, these two drugs reduce the tremor severity by only half. In medication refractory and functionally disabling tremor, alternative forms of therapy need to be considered. Botulinum toxin injections are likely efficacious for limb, voice and head tremor but are associated with side effects. Surgical interventions include deep brain stimulation; magnetic resonance-guided focused ultrasound and thalamotomy for unilateral and deep brain stimulation for bilateral procedures. Recent consensus classification for essential tremor has included a new subgroup, ‘Essential tremor plus’, who have associated subtle neurological ‘soft signs’, such as dystonic posturing of limbs and may require a different treatment approach. In this review, we have addressed the current management of essential tremor with regard to different anatomical locations of tremor as well as different modalities of treatment.
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47
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Cagnan H, Denison T, McIntyre C, Brown P. Emerging technologies for improved deep brain stimulation. Nat Biotechnol 2019; 37:1024-1033. [PMID: 31477926 PMCID: PMC6877347 DOI: 10.1038/s41587-019-0244-6] [Citation(s) in RCA: 151] [Impact Index Per Article: 25.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Accepted: 07/26/2019] [Indexed: 12/18/2022]
Abstract
Deep brain stimulation (DBS) is an effective treatment for common movement disorders and has been used to modulate neural activity through delivery of electrical stimulation to key brain structures. The long-term efficacy of stimulation in treating disorders, such as Parkinson's disease and essential tremor, has encouraged its application to a wide range of neurological and psychiatric conditions. Nevertheless, adoption of DBS remains limited, even in Parkinson's disease. Recent failed clinical trials of DBS in major depression, and modest treatment outcomes in dementia and epilepsy, are spurring further development. These improvements focus on interaction with disease circuits through complementary, spatially and temporally specific approaches. Spatial specificity is promoted by the use of segmented electrodes and field steering, and temporal specificity involves the delivery of patterned stimulation, mostly controlled through disease-related feedback. Underpinning these developments are new insights into brain structure-function relationships and aberrant circuit dynamics, including new methods with which to assess and refine the clinical effects of stimulation.
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Affiliation(s)
- Hayriye Cagnan
- MRC Brain Network Dynamics Unit, University of Oxford, Oxford, UK.
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
| | - Timothy Denison
- MRC Brain Network Dynamics Unit, University of Oxford, Oxford, UK
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
- Department of Engineering Sciences, University of Oxford, Oxford, UK
| | - Cameron McIntyre
- School of Medicine, Case Western Reserve University, Cleveland, OH, USA
| | - Peter Brown
- MRC Brain Network Dynamics Unit, University of Oxford, Oxford, UK
- Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
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48
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Fasano A, Helmich RC. Tremor habituation to deep brain stimulation: Underlying mechanisms and solutions. Mov Disord 2019; 34:1761-1773. [PMID: 31433906 DOI: 10.1002/mds.27821] [Citation(s) in RCA: 62] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2019] [Revised: 07/01/2019] [Accepted: 07/18/2019] [Indexed: 12/14/2022] Open
Abstract
DBS of the ventral intermediate nucleus is an extremely effective treatment for essential tremor, although a waning benefit is observed after a variable time in a variable proportion of patients (ranging from 0% to 73%), a concept historically defined as "tolerance." Tolerance is currently an established concept in the medical community, although there is debate on its real existence. In fact, very few publications have actually addressed the problem, thus making tolerance a typical example of science based on "eminence rather than evidence." The underpinnings of the phenomena associated with the progressive loss of DBS benefit are not fully elucidated, although the interplay of different-not mutually exclusive-factors has been advocated. In this viewpoint, we gathered the evidence explaining the progressive loss of benefit observed after DBS. We grouped these factors in three categories: disease-related factors (tremor etiology and progression); surgery-related factors (electrode location, microlesional effect and placebo); and stimulation-related factors (not optimized stimulation, stimulation-induced side effects, habituation, and tremor rebound). We also propose possible pathophysiological explanations for the phenomenon and define a nomenclature of the associated features: early versus late DBS failure; tremor rebound versus habituation (to be preferred over tolerance). Finally, we provide a practical approach for preventing and treating this loss of DBS benefit, and we draft a possible roadmap for the research to come. © 2019 International Parkinson and Movement Disorder Society.
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Affiliation(s)
- Alfonso Fasano
- Edmond J. Safra Program in Parkinson's Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, UHN, Toronto, Ontario, Canada; Division of Neurology, University of Toronto, Toronto, Ontario, Canada.,Krembil Brain Institute, Toronto, Ontario, Canada.,CenteR for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Ontario, Canada
| | - Rick C Helmich
- Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Nijmegen, The Netherlands
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49
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Mirza KB, Golden CT, Nikolic K, Toumazou C. Closed-Loop Implantable Therapeutic Neuromodulation Systems Based on Neurochemical Monitoring. Front Neurosci 2019; 13:808. [PMID: 31481864 PMCID: PMC6710388 DOI: 10.3389/fnins.2019.00808] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Accepted: 07/19/2019] [Indexed: 12/29/2022] Open
Abstract
Closed-loop or intelligent neuromodulation allows adjustable, personalized neuromodulation which usually incorporates the recording of a biomarker, followed by implementation of an algorithm which decides the timing (when?) and strength (how much?) of stimulation. Closed-loop neuromodulation has been shown to have greater benefits compared to open-loop neuromodulation, particularly for therapeutic applications such as pharmacoresistant epilepsy, movement disorders and potentially for psychological disorders such as depression or drug addiction. However, an important aspect of the technique is selection of an appropriate, preferably neural biomarker. Neurochemical sensing can provide high resolution biomarker monitoring for various neurological disorders as well as offer deeper insight into neurological mechanisms. The chemicals of interest being measured, could be ions such as potassium (K+), sodium (Na+), calcium (Ca2+), chloride (Cl−), hydrogen (H+) or neurotransmitters such as dopamine, serotonin and glutamate. This review focusses on the different building blocks necessary for a neurochemical, closed-loop neuromodulation system including biomarkers, sensors and data processing algorithms. Furthermore, it also highlights the merits and drawbacks of using this biomarker modality.
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Affiliation(s)
- Khalid B Mirza
- Department of Electrical and Electronic Engineering, Centre for Bio-Inspired Technology, Institute of Biomedical Engineering, Imperial College London, London, United Kingdom
| | - Caroline T Golden
- Department of Electrical and Electronic Engineering, Centre for Bio-Inspired Technology, Institute of Biomedical Engineering, Imperial College London, London, United Kingdom
| | - Konstantin Nikolic
- Department of Electrical and Electronic Engineering, Centre for Bio-Inspired Technology, Institute of Biomedical Engineering, Imperial College London, London, United Kingdom
| | - Christofer Toumazou
- Department of Electrical and Electronic Engineering, Centre for Bio-Inspired Technology, Institute of Biomedical Engineering, Imperial College London, London, United Kingdom
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50
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Milosevic L, Kalia SK, Hodaie M, Lozano AM, Popovic MR, Hutchison WD. Physiological mechanisms of thalamic ventral intermediate nucleus stimulation for tremor suppression. Brain 2019; 141:2142-2155. [PMID: 29878147 PMCID: PMC6022553 DOI: 10.1093/brain/awy139] [Citation(s) in RCA: 89] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2018] [Accepted: 04/05/2018] [Indexed: 11/12/2022] Open
Abstract
Ventral intermediate thalamic deep brain stimulation is a standard therapy for the treatment of medically refractory essential tremor and tremor-dominant Parkinson's disease. Despite the therapeutic benefits, the mechanisms of action are varied and complex, and the pathophysiology and genesis of tremor remain unsubstantiated. This intraoperative study investigated the effects of high frequency microstimulation on both neuronal firing and tremor suppression simultaneously. In each of nine essential tremor and two Parkinson's disease patients who underwent stereotactic neurosurgery, two closely spaced (600 µm) microelectrodes were advanced into the ventral intermediate nucleus. One microelectrode recorded action potential firing while the adjacent electrode delivered stimulation trains at 100 Hz and 200 Hz (2-5 s, 100 µA, 150 µs). A triaxial accelerometer was used to measure postural tremor of the contralateral hand. At 200 Hz, stimulation led to 68 ± 8% (P < 0.001) inhibition of neuronal firing and a 53 ± 5% (P < 0.001) reduction in tremor, while 100 Hz reduced firing by 26 ± 12% (not significant) with a 17 ± 6% (P < 0.05) tremor reduction. The degree of cell inhibition and tremor suppression were significantly correlated (P < 0.001). We also found that the most ventroposterior stimulation sites, closest to the border of the ventral caudal nucleus, had the best effect on tremor. Finally, prior to the inhibition of neuronal firing, microstimulation caused a transient driving of neuronal activity at stimulus onset (61% of sites), which gave rise to a tremor phase reset (73% of these sites). This was likely due to activation of the excitatory glutamatergic cortical and cerebellar afferents to the ventral intermediate nucleus. Temporal characteristics of the driving responses (duration, number of spikes, and onset latency) significantly differed between 100 Hz and 200 Hz stimulation trains. The subsequent inhibition of neuronal activity was likely due to synaptic fatigue. Thalamic neuronal inhibition seems necessary for tremor reduction and may function in effect as a thalamic filter to uncouple thalamo-cortical from cortico-spinal reflex loops. Additionally, our findings shed light on the gating properties of the ventral intermediate nucleus within the cerebello-thalamo-cortical tremor network, provide insight for the optimization of deep brain stimulation technologies, and may inform controlled clinical studies for assessing optimal target locations for the treatment of tremor.
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Affiliation(s)
- Luka Milosevic
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.,Rehabilitation Engineering Laboratory, Toronto Rehabilitation Institute - University Health Network, Toronto, Canada
| | - Suneil K Kalia
- Department of Surgery, University of Toronto, Toronto, Canada.,Division of Neurosurgery, Toronto Western Hospital - University Health Network, Toronto, Canada.,Krembil Research Institute, Toronto, Canada
| | - Mojgan Hodaie
- Department of Surgery, University of Toronto, Toronto, Canada.,Division of Neurosurgery, Toronto Western Hospital - University Health Network, Toronto, Canada.,Krembil Research Institute, Toronto, Canada
| | - Andres M Lozano
- Department of Surgery, University of Toronto, Toronto, Canada.,Division of Neurosurgery, Toronto Western Hospital - University Health Network, Toronto, Canada.,Krembil Research Institute, Toronto, Canada
| | - Milos R Popovic
- Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Canada.,Rehabilitation Engineering Laboratory, Toronto Rehabilitation Institute - University Health Network, Toronto, Canada
| | - William D Hutchison
- Department of Surgery, University of Toronto, Toronto, Canada.,Krembil Research Institute, Toronto, Canada.,Department of Physiology, University of Toronto, Toronto, Canada
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