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1.
  • Abell, T. L., et al. (author)
  • Neurostimulation of the Gastrointestinal Tract: Review of Recent Developments
  • 2015
  • In: Neuromodulation. - : Elsevier BV. - 1094-7159. ; 18:3, s. 221-227
  • Journal article (peer-reviewed)abstract
    • ObjectiveNeurostimulation is one manifestation of neuromodulation of the gastrointestinal (GI) tract. This manuscript reviews the history of neurostimulation of the GI tract with emphasis on current methods of stimulation. Materials and MethodsA review was completed of the current research on GI neurostimulation methods with an emphasis on their clinical applications. ResultsUpper GI disorders can be modulated with both temporary (placed endoscopically or surgically) or permanent (placed surgically) gastric electrical stimulation (GES) devices. The current GI neurostimulation of stomach (GES) devices have been used in both children and adults, and some patients have been followed in excess of 15 years with good long-term results. Similar GES devices also have been used for a variety of lower GI disorders, including constipation and fecal incontinence, for a number of years. ConclusionsGI neurostimulation, as a type of neuromodulation, has been demonstrated to function at several locations in the GI tract for a variety of disorders. The future of neurostimulation in the GI tract will likely be influenced by a better understanding of pathophysiology as well as the development of new techniques and devices for neuromodulation.
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  • Blomstedt, Patric, et al. (author)
  • Electromagnetic environmental influences on implanted deep brain stimulators
  • 2006
  • In: Neuromodulation. - : Elsevier BV. - 1094-7159 .- 1525-1403. ; 9:4, s. 262-269
  • Journal article (peer-reviewed)abstract
    • Objective.  The objective of this study was to report our observations on the external electromagnetic field influences on deep brain stimulation (DBS) in our patient population and how these influences affected our patients’ lives and other healthcare-related conditions. Materials and Methods.  We have retrospectively analyzed data concerning the effects of external electromagnetic fields on 172 of our patients implanted with DBS. Results.  Identifiable electromagnetic sources turned the implantable pulse generator (IPG) off in 20 patients. In two patients, these episodes necessitated replacement of the Itrel II IPG (Medtronic Inc., Minneapolis, MN, USA) with the magnetically shielded Kinetra IPG (Medtronic Inc.). Six patients received cardiac pacemakers, leading, in two patients, to interference between the systems. Our experience concerning magnetic resonance imaging, electrocardiogram (ECG), heart defibrillation, electro-cautery, and other sources of electromagnetic interference also is described. Conclusions.  External electromagnetic interference may, in rare cases, constitute a severe threat to the well-being of the patient implanted with a DBS system. Also, malfunction of a DBS system may constitute a medical emergency. Nevertheless, in spite of these external electromagnetic influences, we consider DBS to be a safe method, provided safety protocols are followed, and provided that provider awareness about potential hazards is present.
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  • Bäckryd, Emmanuel, et al. (author)
  • Ziconotide Trialing by Intrathecal Bolus Injections: An Open-Label Non-Randomized Clinical Trial in Postoperative/Posttraumatic Neuropathic Pain Patients Refractory to Conventional Treatment
  • 2015
  • In: Neuromodulation. - : Wiley. - 1094-7159 .- 1525-1403. ; 18:5, s. 404-413
  • Journal article (peer-reviewed)abstract
    • Objectives: The aim of this open-label, non-randomized, clinical trial was to evaluate the feasibility of trialing ziconotide by intrathecal bolus injections. Material and Methods: Twenty-three patients, who had peripheral neuropathic pain refractory to pharmacological treatment and were under consideration for Spinal Cord Stimulation, received up to three ziconotide bolus injections according to a comprehensive algorithm. After a first injection of 2.5g, the patients progressed in the algorithm depending on the presence or absence of pain reduction and significant adverse events. A patient was considered a "responder" if experiencing pain reduction and no significant adverse event on two consecutive occasions at the same dosage. Results: We found a low proportion of responders (13%). However 30% of patients experienced greater than= 30% pain reduction on a least one injection, yielding a number needed to treat of similar to 3 for clinically significant pain relief. Pain intensity changed significantly over time (0-6h) (p = 0.047) after a mean ziconotide dose of 2.75 mu g. Adverse events were as expected, and no serious adverse event occurred. We did not find any statistical association between response to Spinal Cord Stimulation and response to ziconotide. Conclusions: Ziconotide bolus injection trialing seems feasible, but the proportion of responders in the present study was low. Adverse events were as expected, and no serious adverse event occurred. The predictive power of ziconotide bolus trialing remains unclear, and the pharmacological profile of ziconotide (slow tissue penetration due to high hydrophilicity) calls the rationale for bolus trialing into question.
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  • Hariz, Gun-Marie, et al. (author)
  • Perceptions of living with a device-based treatment : an account of patients treated with deep brain stimulation for Parkinson’s disease
  • 2014
  • In: Neuromodulation. - : Elsevier BV. - 1094-7159 .- 1525-1403. ; 17:3, s. 272-278
  • Journal article (peer-reviewed)abstract
    • Objectives Deep brain stimulation (DBS) is an established treatment for Parkinson's disease. Little is known about patients' own perceptions of living with the implanted hardware. We aimed to explore patients' own perceptions of living with an implanted device. Materials and Methods Semistructured interviews with open-ended questions were conducted with 42 patients (11 women) who had been on DBS for a mean of three years. The questions focused on patients' experiences of living with and managing the DBS device. The interviews were transcribed verbatim and analyzed according to the difference and similarity technique in grounded theory. Results From the patients' narratives concerning living with and managing the DBS device, the following four categories emerged: 1) The device—not a big issue: although the hardware was felt inside the body and also visible from outside, the device as such was not a big issue. 2) Necessary carefulness: Patients expressed the need to be careful when performing certain daily activities in order not to dislocate or harm the device. 3) Continuous need for professional support: Most patients relied solely on professionals for fine-tuning the stimulation rather than using their handheld controller, even if this entailed numerous visits to a remote hospital. 4) Balancing symptom relief and side-effects: Patients expressed difficulties in finding the optimal match between decrease of symptoms and stimulation-induced side-effects. Conclusions The in-depth interviews of patients on chronic DBS about their perceptions of living with an implanted device provided useful insights that would be difficult to capture by quantitative evaluations.
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  • Jiltsova, Elena, et al. (author)
  • Imaging of Anterior Nucleus of Thalamus Using 1.5T MRI for Deep Brain Stimulation Targeting in Refractory Epilepsy
  • 2016
  • In: Neuromodulation. - : Elsevier BV. - 1094-7159 .- 1525-1403. ; 19:8, s. 812-817
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Deep brain stimulation (DBS) of the anterior nucleus of thalamus (ANT) is an evolving treatment option in refractory focal epilepsy. Due to poor visualization of ANT in traditional MRI sequences used for movement disorder surgery, targeting of ANT is mainly based on stereotactic atlas information. Sophisticated 3T MRI methods enable visualization of ANT, but 1.5T MRI is still preferred or more readily available in a large number of centers performing DBS.OBJECTIVE: In the present study, we sought to determine whether ANT could be adequately visualized at 1.5T MRI pre- and postoperatively using imaging techniques similar to the ones visualizing ANT in 3T MRI. A total of 15 MRI examinations with short tau inversion recovery (STIR) and T1-weighted magnetization prepared gradient echo (MPRAGE) images were performed to visualize ANT in nonepileptic subjects (n = 2), patients with vagus nerve stimulator (VNS) (n = 3), stereotactic MRI (n = 3), patients with ANT-DBS (n = 7).RESULTS: ANT was distinctly visualized in STIR and T1-weighted MPRAGE images in patients without implanted stimulators, with Leksell stereotactic frame and with fully implanted VNS. Postoperative 1.5T MRI was able to demonstrate some of the anatomical landmarks around ANT enabling assessment of electrode contact locations.CONCLUSIONS: The visualization of ANT is possible in preoperative 1.5T MRI enabling direct targeting of ANT all examined situations. The use of indirect targeting and its inherent potential for lead misplacement due to anatomical variation may be avoided using these MRI methods. Furthermore, postoperative MRI with STIR and T1-weighted MPRAGE images enable detailed postoperative assessment of contact locations.
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  • Jonsson, Emma, et al. (author)
  • Cost and Health Outcomes Patterns in Patients Treated With Spinal Cord Stimulation Following Spine Surgery : A Register-Based Study
  • 2020
  • In: Neuromodulation. - : Elsevier BV. - 1094-7159 .- 1525-1403. ; 23:5, s. 626-633
  • Journal article (peer-reviewed)abstract
    • ObjectiveSpinal cord stimulation (SCS), a minimally invasive treatment option for long‐term neuropathic pain, has been shown to be effective in patients with persisting neuropathic pain after spine surgery. However, little is known about the long‐term cost and quality‐of‐life (QoL) patterns in SCS‐treated patients. The aim is to describe the use of SCS, costs, pre‐spine‐surgery and post‐spine‐surgery QoL, and reported pain intensity, in patients who have undergone spine surgery and subsequent SCS implantation. The results will be related to outcome and cost in spine surgery patients in general.Materials and MethodsA research database comprised from six Swedish national and regional registers, and the spine surgery quality‐of‐care register Swespine was utilized. Two cohorts were identified: all patients who had spine surgery (N = 73,765) and patients who had spine surgery and subsequent SCS implantation (N = 239). Costs were analyzed before and after spine surgery for both cohorts, as well as before and after SCS implantation for the second cohort. QoL was explored by estimating patient‐reported outcome measures such as pain intensity, Oswestry Disability Index, and EuroQol‐5Dimensions from spine surgery up to five years post–spine surgery.ResultsIn spine surgery patients, mean QoL and pain intensity levels improved following surgery. Patients subsequently treated with SCS had lower reported QoL and higher costs before the initial spine surgery, and spine surgery did not lead to any substantial improvements, however, costs decreased following SCS implantation in these patients.
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  • Lind, Anne-Li, et al. (author)
  • Spinal Cord Stimulation Alters Protein Levels in the Cerebrospinal Fluid of Neuropathic Pain Patients : A Proteomic Mass Spectrometric Analysis
  • 2016
  • In: Neuromodulation. - : Elsevier BV. - 1094-7159 .- 1525-1403. ; 19:6, s. 549-562
  • Journal article (peer-reviewed)abstract
    • ObjectivesElectrical neuromodulation by spinal cord stimulation (SCS) is a well-established method for treatment of neuropathic pain. However, the mechanism behind the pain relieving effect in patients remains largely unknown. In this study, we target the human cerebrospinal fluid (CSF) proteome, a little investigated aspect of SCS mechanism of action. MethodsTwo different proteomic mass spectrometry protocols were used to analyze the CSF of 14 SCS responsive neuropathic pain patients. Each patient acted as his or her own control and protein content was compared when the stimulator was turned off for 48 hours, and after the stimulator had been used as normal for three weeks. ResultsEighty-six proteins were statistically significantly altered in the CSF of neuropathic pain patients using SCS, when comparing the stimulator off condition to the stimulator on condition. The top 12 of the altered proteins are involved in neuroprotection (clusterin, gelsolin, mimecan, angiotensinogen, secretogranin-1, amyloid beta A4 protein), synaptic plasticity/learning/memory (gelsolin, apolipoprotein C1, apolipoprotein E, contactin-1, neural cell adhesion molecule L1-like protein), nociceptive signaling (neurosecretory protein VGF), and immune regulation (dickkopf-related protein 3). ConclusionPreviously unknown effects of SCS on levels of proteins involved in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity are demonstrated. These findings, in the CSF of neuropathic pain patients, expand the picture of SCS effects on the neurochemical environment of the human spinal cord. An improved understanding of SCS mechanism may lead to new tracks of investigation and improved treatment strategies for neuropathic pain.
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  • Linderoth, Bengt, et al. (author)
  • Bjorn Meyerson 1933-2019 OBITUARY
  • 2020
  • In: Neuromodulation. - : John Wiley & Sons. - 1094-7159 .- 1525-1403. ; 23:1, s. 1-2
  • Journal article (other academic/artistic)
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  • Mai, Junyan, et al. (author)
  • Prolonged Inhibitory Effects of Repeated Tibial Nerve Stimulation on the Micturition Reflex in Decorticated Rats
  • 2022
  • In: Neuromodulation. - : ELSEVIER. - 1094-7159 .- 1525-1403. ; 25:8, s. 1115-1121
  • Journal article (peer-reviewed)abstract
    • Objective: This study aimed to determine whether a short-term repeated stimulation of tibial nerve afferents induces a prolonged modulation effect on the micturition reflex in a decorticated rat model. Material and Methods: Fifteen female Sprague-Dawley rats (250-350 g) were fully decorticated and paralyzed in the study. Tibial nerve stimulation (TNS) was delivered by inserting two pairs of needle electrodes close to the nerves at the level of the medial malleolus. Constant flow cystometries (0.07 mL/min) at approximately ten-minute intervals were performed, and the micturition threshold volume (MTV) was recorded and used as a dependent variable. After four to five stable recordings, the tibial nerves of both sides were stimulated continuously for five minutes at 10 Hz and at an intensity of three times the threshold for alpha-motor axons. Six same stimulations were applied repeatedly, with an interval of five minutes between each stimulation. Mean MTV was calculated on the basis of several cystometries in each half-hour period before, during, and after the six repeated TNS. Results: During the experiment, all the animals survived in good condition with relatively stable micturition reflexes, and a significant increase in MTV was detected after TNS. The strongest effect (mean = 178%) was observed during the first 30 minutes after six repeated stimulations. This obvious threshold increase remained for at least five hours. Conclusions: A prolonged poststimulation modulatory effect on the micturition reflex was induced by short-term repeated TNS in decorticated rats. This study provides a theoretical explanation for the clinical benefit of TNS in patients with overactive bladder and suggests decorticated rats as a promising model for further investigation of the neurophysiological mechanisms underlying the bladder inhibitory response induced by TNS.
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  • Revesz, David, et al. (author)
  • Estimating Long-Term Vagus Nerve Stimulation Effectiveness: Accounting for Antiepileptic Drug Treatment Changes
  • 2018
  • In: Neuromodulation. - : Elsevier BV. - 1094-7159. ; 21:8, s. 797-804
  • Journal article (peer-reviewed)abstract
    • Objective To investigate the effectiveness of vagus nerve stimulation (VNS) in combination with pharmacological therapy in a longitudinal retrospective study at a single center. Materials and Methods Data from 130 consecutive patients implanted with a VNS device between the years 2000 and 2013 was analyzed. Seizure frequency and pharmacological antiepileptic drug (AED) treatments were recorded prior to as well as at one, two, and five years after VNS implantation. Results Median age at epilepsy onset was five years and mean years from diagnosis to VNS implantation was 16.5 years. There was a significant seizure reduction overall (all p < 0.001). The responder (>= 50% seizure frequency reduction) rate increased from 22.1 to 43.8% between the first and fifth year for the cohort as a whole, with the largest increase between the first and second year (22.1-38.1%) and regardless of AED changes. VNS effectiveness did not differ between patients who altered or remained on the same AEDs. Patients were treated with a median of three AEDs throughout the study and the number of AEDs significantly increased after two (p = 0.007) and five (p = 0.001) years. Conclusions VNS is a well-tolerated palliative neuromodulatory treatment for drug resistant epilepsy with a 43.8% seizure reduction after five years. Our data supports the idea that VNS effectiveness increases with time. Therefore we suggest that VNS should be evaluated for at least two years after implantation. AED changes should try to be kept to a minimum during evaluation in order to determine the effectiveness of VNS.
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  • Stenmark Persson, Rasmus, et al. (author)
  • Deep Brain Stimulation of Caudal Zona Incerta for Parkinson's Disease : One-Year Follow-Up and Electric Field Simulations
  • 2022
  • In: Neuromodulation. - : Elsevier. - 1094-7159 .- 1525-1403. ; 25:6, s. 935-944
  • Journal article (peer-reviewed)abstract
    • Objective: To evaluate the effects of bilateral caudal zona incerta (cZi) deep brain stimulation (DBS) for Parkinson's disease (PD) one year after surgery and to create anatomical improvement maps based on patient-specific simulation of the electric field.Materials and Methods: We report the one-year results of bilateral cZi-DBS in 15 patients with PD. Patients were evaluated on/off medication and stimulation using the Unified Parkinson's Disease Rating Scale (UPDRS). Main outcomes were changes in motor symptoms (UPDRS-III) and quality of life according to Parkinson's Disease Questionnaire-39 (PDQ-39). Secondary outcomes included efficacy profile according to sub-items of UPDRS-III, and simulation of the electric field distribution around the DBS lead using the finite element method. Simulations from all patients were transformed to one common magnetic resonance imaging template space for creation of improvement maps and anatomical evaluation.Results: Median UPDRS-III score off medication improved from 40 at baseline to 21 on stimulation at one-year follow-up (48%, p < 0.0005). PDQ-39 summary index did not change but the subdomains activities of daily living (ADL) and stigma improved (25%, p < 0.03 and 75%, p < 0.01), whereas communication worsened (p < 0.03). For UPDRS-III sub-items, stimulation alone reduced median tremor score by 9 points, akinesia by 3, and rigidity by 2 points at one-year follow-up in comparison to baseline (90%, 25%, and 29% respectively, p < 0.01). Visual analysis of the anatomical improvement maps based on simulated electrical fields showed no evident relation with the degree of symptom improvement and neither did statistical analysis show any significant correlation.Conclusions: Bilateral cZi-DBS alleviates motor symptoms, especially tremor, and improves ADL and stigma in PD patients one year after surgery. Improvement maps may be a useful tool for visualizing the spread of the electric field. However, there was no clear-cut relation between anatomical location of the electric field and the degree of symptom relief.
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  • Tabatabaei, Pedram, et al. (author)
  • Bilateral T12 dorsal root ganglion stimulation for the treatment of low back pain with 20-Hz and 4-Hz stimulation : a retrospective study
  • 2024
  • In: Neuromodulation. - : Elsevier. - 1094-7159 .- 1525-1403. ; 27:1, s. 141-150
  • Journal article (peer-reviewed)abstract
    • Objectives: Chronic low back pain (CLBP) is one of the most common chronic pain conditions that cause both individual suffering and a burden to society. For these patients, several interventional treatment options such as surgery, blocks, radiofrequency, and spinal cord stimulation are available. Lately, dorsal root ganglion stimulation (DRG-S) also has been mentioned as an option by targeting bilateral T12 dorsal ganglia. In this study, we present the outcome of 11 patients with CLBP treated with bilateral T12 DRG-S.Materials and Methods: Thirteen patients with CLBP with and without leg pain were treated with bilateral T12 DRG-S. Three of the patients also received a third lumbar lead owing to leg pain. Eleven of the patients had >50% pain relief during the peri- or/and postoperative testing and received a fully implantable neurostimulator. Pain intensity, general health status, quality of life, pain catastrophizing, mental status, sleeping disorder, physical activity, and patient satisfaction were followed using numeric rating scale (NRS), Patient-Reported Outcomes Measurement Information System 29 version 2.1, Pain Catastrophizing Score, Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire Depression Module, Insomnia Severity Index, and Patient Satisfaction Questionnaire at baseline before implantation and at three months and six months. The results were analyzed on the basis of six domains: pain relief, sleeping disorder, social ability, mental status, physical activity, and satisfaction. To be identified as a responder, the patients should show a significant improvement in the pain relief domain together with at least two other domains. All responders also were given the opportunity to test 4-Hz DRG-S and compare it with traditional 20-Hz stimulation.Results: All 11 patients were identified as responders at six months. Five of the patients had >80% pain relief, with an average NRS score reduction of 71% for the whole group. Significant improvement could be observed in three domains for one patient, four domains for three patients, five domains for six patients, and six domains for one patient. Seven patients chose to try 4-Hz stimulation. All seven identified 4-Hz stimulation as at least as good as or better than 20-Hz stimulation and chose to continue with 4-Hz stimulation.Conclusions: Bilateral T12 DRG-S seems to be an effective treatment for chronic low back pain, with significant beneficial effect not only on pain but also on quality of life, pain catastrophizing, mental status, sleeping disorder, and physical activity. 4-Hz DRG-S gave a result comparable with or better than 20-Hz stimulation.
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  • Wårdell, Karin, et al. (author)
  • Deep Brain Stimulation of the Pallidum Internum for Gilles de la Tourette Syndrome : A Patient-Specific Model-Based Simulation Study of the Electric Field
  • 2015
  • In: Neuromodulation. - : John Wiley & Sons. - 1094-7159 .- 1525-1403. ; :2, s. 90-96
  • Journal article (peer-reviewed)abstract
    • ObjectivesThe aim of this study was to investigate the deep brain stimulation (DBS) electric field distribution in proton-density MRI scans visualizing the globus pallidus internus (GPi) of patients with Gilles de la Tourette syndrome (GTS), along with its relation to the anatomy.MethodsPatient-specific brain tissue models (n = 7) with bilateral DBS electrodes in the GPi were set up using the finite element method in five patients who had undergone stereotactic proton-density MRI-guided surgery and showed variable improvement with DBS. Simulations (n = 27) of the electric field were performed and the results visualized on the respective preoperative stereotactic MRI scans. The mean electric field volumes (n = 81) within the 0.1, 0.15, and 0.2 V/mm isosurfaces were calculated and compared with the anatomy.ResultsVisualization of the simulated electric field confirmed that the anteromedial limbic GPi was the main stimulated target for four of the patients and the posteromedial sensorimotor GPi for one. Larger volumes extended asymmetrically, with parts of fields stretching into the lamina between GPi and globus pallidus externus and into the internal capsule. There was a high correlation (r = 0.994, n = 54) between volumes and brain sides, but with a systematic shift toward the right side, especially for the larger volumes. Simulations with homogeneous tissue models showed no differences.ConclusionsPatient-specific DBS electric field simulations in the GPi as visualized on proton-density MR scans can be implemented in patients with GTS. Visualization of electric fields together with stereotactic thin-slice MRI can provide further support when predicting anatomical structures possibly influenced by DBS in this complex disorder.
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  • Zsigmond, Peter, 1966-, et al. (author)
  • Proteomic Analysis of the Cerebrospinal Fluid in Patients With Essential Tremor Before and After Deep Brain Stimulation Surgery: A Pilot Study
  • 2020
  • In: Neuromodulation. - : WILEY. - 1094-7159 .- 1525-1403. ; 23:4, s. 502-508
  • Journal article (peer-reviewed)abstract
    • Objective Electrical neuromodulation by deep brain stimulation (DBS) is a well-established method for treatment of severe essential tremor (ET). The mechanism behind the tremor relieving effect remains largely unknown. Our aim of this study was to evaluate alterations in proteomics pre- and post-DBS in patients diagnosed with severe ET. Materials and Methods Ten right-handed ET patients were included in this study. Cerebrospinal fluid (CSF) was obtained by lumbar puncture preoperatively (N = 10) and six months postoperatively (N = 7). The samples were analyzed by high sensitive liquid chromatography tandem mass spectrometry. Results Twenty-two proteins were statistically significantly altered in the CSF of ET patients before and after DBS treatment. Downregulated proteins were involved in regulatory processes of protein activation, complement activation, humoral immune response as well as acute inflammatory response. The upregulated proteins were involved in pathways for cell secretion, adhesion as well as response to axon injury. Conclusions DBS in ET patients effects the neurochemical environment in the CSF. These findings further elucidate the mechanisms of DBS and may lead to new biomarkers for evaluating the effect of DBS treatment.
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