P.089 Ultra-high frequency deep brain stimulation at 10,000 Hz improves motor function

Background: Stimulation frequency has been considered a crucial determinant of efficacy in deep brain stimulation (DBS). DBS at frequencies over 250Hz is not currently employed and consensus in the field suggests that higher frequencies are not clinically effective. With the recent demonstration of clinically effective ultra-high frequency (UHF) spinal cord stimulation at 10kHz we tested whether UHF stimulation could also be clinically useful in movement disorder patients with DBS. Methods: We studied the effects of conventional (130Hz) and UHF stimulation in five patients with Parkinson’s disease (PD) with STN DBS and in one patient with essential tremor (ET) with VIM DBS. We compared the clinical benefit and adverse effects of stimulation at various amplitudes either intraoperatively or postoperatively with the electrodes externalized. Results: Motor performance improved in all six patients with UHF DBS. 10kHz stimulation at amplitudes ≥3.0mA appeared to be as effective as 130Hz in improving motor symptoms (46.2% vs 53.5% motor score reduction, p=0.110, N=90 trials). Interestingly, 10kHz stimulation resulted in fewer stimulation-induced paresthesiae and speech adverse effects than 130Hz stimulation. Conclusions: Our results indicate that DBS at 10kHz produces clinical benefits while possibly reducing stimulation-induced adverse effects in patients with movement disorders.

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Intraoperative Characterization of Subthalamic Nucleus-to-Cortex Evoked Potentials in Parkinson’s Disease Deep Brain Stimulation

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.590251 ◽

2021 ◽

Vol 15 ◽

Author(s):

Lila H. Levinson ◽

David J. Caldwell ◽

Jeneva A. Cronin ◽

Brady Houston ◽

Steve I. Perlmutter ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Evoked Potentials ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

High Frequency ◽

Therapeutic Effects ◽

Stn Dbs ◽

Deep Brain

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a clinically effective tool for treating medically refractory Parkinson’s disease (PD), but its neural mechanisms remain debated. Previous work has demonstrated that STN DBS results in evoked potentials (EPs) in the primary motor cortex (M1), suggesting that modulation of cortical physiology may be involved in its therapeutic effects. Due to technical challenges presented by high-amplitude DBS artifacts, these EPs are often measured in response to low-frequency stimulation, which is generally ineffective at PD symptom management. This study aims to characterize STN-to-cortex EPs seen during clinically relevant high-frequency STN DBS for PD. Intraoperatively, we applied STN DBS to 6 PD patients while recording electrocorticography (ECoG) from an electrode strip over the ipsilateral central sulcus. Using recently published techniques, we removed large stimulation artifacts to enable quantification of STN-to-cortex EPs. Two cortical EPs were observed – one synchronized with DBS onset and persisting during ongoing stimulation, and one immediately following DBS offset, here termed the “start” and the “end” EPs respectively. The start EP is, to our knowledge, the first long-latency cortical EP reported during ongoing high-frequency DBS. The start and end EPs differ in magnitude (p < 0.05) and latency (p < 0.001), and the end, but not the start, EP magnitude has a significant relationship (p < 0.001, adjusted for random effects of subject) to ongoing high gamma (80–150 Hz) power during the EP. These contrasts may suggest mechanistic or circuit differences in EP production during the two time periods. This represents a potential framework for relating DBS clinical efficacy to the effects of a variety of stimulation parameters on EPs.

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Comparison of Subthalamic Nucleus and Globus Pallidus Deep Brain Stimulation in Parkinson’s Disease: A Systematic Review

Austin Alzheimer's and Parkinson's Disease ◽

10.26420/austinalzheimersjparkinsonsdis.2021.1033 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Azari H ◽

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Adverse Effects ◽

Globus Pallidus ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Stn Dbs ◽

Deep Brain

Background: Deep Brain Stimulation (DBS) is regarded as a viable therapeutic choice for Parkinson’s Disease (PD). The two most common sites for DBS are the Subthalamic Nucleus (STN) and Globus Pallidus (GPi). In this study, the clinical effectiveness of these two targets was compared. Methods: A systematic literature search in electronic databases were restricted to English language publications 2010 to 2021. Specified MeSH terms were searched in all databases. Studies that evaluated the Unified Parkinson’s Disease Rating Scale (UPDRS) III were selected by meeting the following criteria: (1) had at least three months follow-up period; (2) compared both GPi and STN DBS; (3) at least five participants in each group; (4) conducted after 2010. Study quality assessment was performed using the Modified Jadad Scale. Results: 3577 potentially relevant articles were identified 3569 were excluded based on title and abstract, duplicate and unsuitable article removal. Eight articles satisfied the inclusion criteria and were scrutinized (458 PD patients). Majority of studies reported no statistically significant between-group difference for improvements in UPDRS III scores. Conclusions: Although there were some results in terms of action tremor, rigidity, and urinary symptoms, which indicated that STN DBS might be a better choice or regarding the adverse effects, GPi seemed better; but it cannot be concluded that one target is superior. Other larger randomized clinical trials with longer follow-up periods and control groups are needed to decide which target is more efficient for stimulation and imposes fewer adverse effects on the patients.

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Introduction to Deep Brain Stimulation

Neurosurgical FOCUS ◽

10.3171/2017.2.focusvid.intro ◽

2017 ◽

Vol 42 (videosuppl2) ◽

pp. Intro ◽

Cited By ~ 2

Author(s):

Andres M. Lozano ◽

Robert E. Gross

Keyword(s):

Deep Brain Stimulation ◽

Adverse Effects ◽

Brain Stimulation ◽

Movement Disorders ◽

Surgical Techniques ◽

Single Target ◽

Holmes Tremor ◽

Clinical Benefits ◽

Technical Details ◽

Deep Brain

It is estimated that over 160,000 patients worldwide have received deep brain stimulation (DBS) to date predominantly for Parkinson's disease and other movement disorders. With the success of this therapy, a greater appreciation of the clinical benefits and adverse effects is being realized. Neurosurgeons are increasingly paying attention to the technical details of these procedures and optimizing targeting, surgical techniques, and programming to improve outcomes.In this issue, the nuances of surgical techniques for DBS are covered by Dr. House. Dr. Toda et al. and Mr. Chartrain et al. tackle the approach to treating tremors, either essential tremor or Holmes tremor, using either a single target or, in cases of difficult-to-treat tremors, using more than one target and interleaving the stimulation. These abstracts and videos will be appreciated by both those who are being initiated to DBS and the more seasoned practitioners who are looking for helpful hints to tackle challenging cases.

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Comparison of subthalamic nucleus and globus pallidus deep brain stimulation in patients with Parkinson's disease: A systematic review of literature

10.21203/rs.3.rs-923706/v1 ◽

2021 ◽

Author(s):

Hushyar Azari

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Adverse Effects ◽

Globus Pallidus ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Stn Dbs ◽

Deep Brain

Abstract Background: Deep brain stimulation (DBS) is regarded as a viable therapeutic choice for Parkinson's disease (PD). The two most common sites for DBS are the subthalamic nucleus (STN) and globus pallidus (GPi). In this study, the clinical effectiveness of these two targets was compared.Methods: A systematic literature search in electronic databases were restricted to English language publications 2010 to 2021. Specified MeSH terms were searched in all databases. Studies that evaluated the Unified Parkinson's Disease Rating Scale (UPDRS) III were selected by meeting the following criteria: (1) had at least three months follow-up period; (2) compared both GPi and STN DBS; (3)at least five participants in each group; (4)conducted after 2010. Study quality assessment was performed using the Modified Jadad Scale.Results: 3577 potentially relevant articles were identified,3569 were excluded based on title and abstract, duplicate and unsuitable article removal. Eight articles satisfied the inclusion criteria and were scrutinized (458 PD patients). Majority of studies reported no statistically significant between-group difference for improvements in UPDRS ш scores.Conclusions: Although there were some results in terms of action tremor, rigidity, and urinary symptoms, which indicated that STN DBS might be a better choice or regarding the adverse effects, GPi seemed better; but it cannot be concluded that one target is superior. Other larger randomized clinical trials with longer follow-up periods and control groups are needed to decide which target is more efficient for stimulation and imposes fewer adverse effects on the patients.

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Ultrahigh Frequency Deep Brain Stimulation at 10 000 Hz Improves Motor Function

Neurosurgery ◽

10.1093/neuros/nyz310_367 ◽

2019 ◽

Vol 66 (Supplement_1) ◽

Author(s):

Irene E Harmsen ◽

Darrin J Lee ◽

Robert F Dallapiazza ◽

Philippe De Vloo ◽

Robert Chen ◽

...

Keyword(s):

Spinal Cord ◽

Deep Brain Stimulation ◽

Adverse Effects ◽

Brain Stimulation ◽

Spinal Cord Stimulation ◽

Ultrahigh Frequency ◽

Clinical Effects ◽

Stimulation Parameters ◽

Clinical Benefits ◽

Deep Brain

Abstract INTRODUCTION Stimulation frequency has been considered a crucial determinant of efficacy in deep brain stimulation (DBS). DBS at frequencies over 250 Hz is not currently employed and consensus in the field suggests that higher frequencies are not clinically effective. With the recent demonstration of clinically effective ultrahigh frequency (UHF) spinal cord stimulation at 10 kHz we tested whether UHF stimulation could also be clinically useful in movement disorder patients with DBS. We evaluated the clinical effects and safety of UHF DBS in patients with subthalamic nucleus (STN) or ventral intermediate thalamic nucleus (VIM) DBS. METHODS We studied the effects of conventional (130 Hz) and UHF stimulation in 5 patients with Parkinson's disease (PD) with STN DBS and in one patient with essential tremor (ET) with VIM DBS. We compared the clinical benefit and adverse effects of stimulation at various amplitudes either intraoperatively or postoperatively with the electrodes externalized. RESULTS Motor performance improved in all 6 patients with UHF DBS. About 10 kHz stimulation at amplitudes = 3.0 mA appeared to be as effective as 130 Hz in improving motor symptoms (46.2% vs 53.5% motor score reduction, P = .110, N = 90 trials). Interestingly, 10 kHz stimulation resulted in fewer stimulation-induced paresthesiae and speech adverse effects than 130 Hz stimulation. CONCLUSION Our results indicate that DBS at 10 kHz produces clinical benefits in patients with movement disorders. Like 10 kHz spinal cord stimulation, 10 kHz DBS has the potential to produce clinical benefits while possibly reducing stimulation-induced adverse effects. Further studies will be required to optimize UHF DBS stimulation parameters and to determine its clinical utility.

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Ultra‐high‐frequency deep brain stimulation at 10,000 Hz improves motor function

Movement Disorders ◽

10.1002/mds.27550 ◽

2018 ◽

Vol 34 (1) ◽

pp. 146-148 ◽

Cited By ~ 3

Author(s):

Irene E. Harmsen ◽

Darrin J. Lee ◽

Robert F. Dallapiazza ◽

Philippe De Vloo ◽

Robert Chen ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Motor Function ◽

Brain Stimulation ◽

High Frequency ◽

Ultra High Frequency ◽

Deep Brain

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Deep Brain Stimulation Frequency of the Subthalamic Nucleus Affects Phonemic and Action Fluency in Parkinson’s Disease

Parkinson s Disease ◽

10.1155/2016/6760243 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 4

Author(s):

Valéria de Carvalho Fagundes ◽

Carlos R. M. Rieder ◽

Aline Nunes da Cruz ◽

Bárbara Costa Beber ◽

Mirna Wetters Portuguez

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

High Frequency ◽

Verbal Fluency ◽

Low Frequency ◽

Stn Dbs ◽

Deep Brain

Introduction.Deep brain stimulation of the subthalamic nucleus (STN-DBS) in Parkinson’s disease (PD) has been linked to a decline in verbal fluency. The decline can be attributed to surgical effects, but the relative contributions of the stimulation parameters are not well understood. This study aimed to investigate the impact of the frequency of STN-DBS on the performance of verbal fluency tasks in patients with PD.Methods.Twenty individuals with PD who received bilateral STN-DBS were evaluated. Their performances of verbal fluency tasks (semantic, phonemic, action, and unconstrained fluencies) upon receiving low-frequency (60 Hz) and high-frequency (130 Hz) STN-DBS were assessed.Results.The performances of phonemic and action fluencies were significantly different between low- and high-frequency STN-DBS. Patients showed a decrease in these verbal fluencies for high-frequency STN-DBS.Conclusion.Low-frequency STN-DBS may be less harmful to the verbal fluency of PD patients.

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Resonant Antidromic Cortical Circuit Activation as a Consequence of High-Frequency Subthalamic Deep-Brain Stimulation

Journal of Neurophysiology ◽

10.1152/jn.00808.2007 ◽

2007 ◽

Vol 98 (6) ◽

pp. 3525-3537 ◽

Cited By ~ 159

Author(s):

S. Li ◽

G. W. Arbuthnott ◽

M. J. Jutras ◽

J. A. Goldberg ◽

D. Jaeger

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

High Frequency ◽

Cortical Neurons ◽

Active Sites ◽

Cortical Activation ◽

Oscillatory Activity ◽

Antidromic Activation ◽

Stn Dbs ◽

Deep Brain

Deep brain stimulation (DBS) is an effective treatment of Parkinson's disease (PD) for many patients. The most effective stimulation consists of high-frequency biphasic stimulation pulses around 130 Hz delivered between two active sites of an implanted depth electrode to the subthalamic nucleus (STN-DBS). Multiple studies have shown that a key effect of STN-DBS that correlates well with clinical outcome is the reduction of synchronous and oscillatory activity in cortical and basal ganglia networks. We hypothesized that antidromic cortical activation may provide an underlying mechanism responsible for this effect, because stimulation is usually performed in proximity to cortical efferent pathways. We show with intracellular cortical recordings in rats that STN-DBS did in fact lead to antidromic spiking of deep layer cortical neurons. Furthermore, antidromic spikes triggered a dampened oscillation of local field potentials in cortex with a resonant frequency around 120 Hz. The amplitude of antidromic activation was significantly correlated with an observed suppression of slow wave and beta band activity during STN-DBS. These findings were seen in ketamine-xylazine or isoflurane anesthesia in both normal and 6-hydroxydopamine (6-OHDA)–lesioned rats. Thus antidromic resonant activation of cortical microcircuits may make an important contribution toward counteracting the overly synchronous and oscillatory activity characteristic of cortical activity in PD.

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Deep Brain Stimulation Treating Dystonia: A Systematic Review of Targets, Body Distributions and Etiology Classifications

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.757579 ◽

2021 ◽

Vol 15 ◽

Author(s):

Houyou Fan ◽

Zijian Zheng ◽

Zixiao Yin ◽

Jianguo Zhang ◽

Guohui Lu

Keyword(s):

Quality Of Life ◽

Deep Brain Stimulation ◽

Adverse Effects ◽

Brain Stimulation ◽

Symptom Improvement ◽

Body Distribution ◽

Stn Dbs ◽

Excellent Improvement ◽

Deep Brain

Background: Deep brain stimulation (DBS) is a typical intervention treating drug-refractory dystonia. Currently, the selection of the better target, the GPi or STN, is debatable. The outcomes of DBS treating dystonia classified by body distribution and etiology is also a popular question.Objective: To comprehensively compare the efficacy, quality of life, mood, and adverse effects (AEs) of GPi-DBS vs. STN-DBS in dystonia as well as in specific types of dystonia classified by body distribution and etiology.Methods: PubMed, Embase, the Cochrane Library, and Google Scholar were searched to identify studies of GPi-DBS and STN-DBS in populations with dystonia. The efficacy, quality of life, mood, and adverse effects were quantitatively compared. Meta-regression analyses were also performed. This analysis has been registered in PROSPERO under the number CRD42020146145.Results: Thirty five studies were included in the main analysis, in which 319 patients underwent GPI-DBS and 113 patients underwent STN-DBS. The average follow-up duration was 12.48 months (range, 3–49 months). The GPI and STN groups were equivalent in terms of efficacy, quality of life, mood, and occurrence of AEs. The focal group demonstrated significantly better disability symptom improvement (P = 0.012) than the segmental and generalized groups but showed less SF-36 enhancement than the segmental group (P < 0.001). The primary groups exhibited significantly better movement and disability symptom improvements than the secondary non-hereditary group (P < 0.005), which demonstrated only disability symptom improvement compared with the secondary hereditary group (P < 0.005). The primary hereditary and idiopathic groups had a significantly lower frequency of AEs than the secondary non-hereditary group (P < 0.005). The correlation between disability symptom improvement and movement symptom improvement was also significant (P < 0.05).Conclusion: GPi-DBS and STN-DBS were both safe and resulted in excellent improvement in efficacy and quality of life in patients with dystonia. Compared with patients with segmental dystonia, patients with focal dystonia demonstrated better improvement in dystonia symptoms but less enhancement of quality of life. Those with primary dystonia had a better response to DBS in terms of efficacy than those with secondary dystonia. Patients who exhibit a significant improvement in movement symptoms might also exhibit excellent improvement in disability symptoms.

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High-fidelity transmission of high-frequency burst stimuli from peripheral nerve to thalamic nuclei in children with dystonia

Scientific Reports ◽

10.1038/s41598-021-88114-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Estefanía Hernandez-Martin ◽

Enrique Arguelles ◽

Yifei Zheng ◽

Ruta Deshpande ◽

Terence D. Sanger

Keyword(s):

Deep Brain Stimulation ◽

Peripheral Nerve ◽

Brain Stimulation ◽

High Frequency ◽

Sensory Information ◽

Brain Structures ◽

High Fidelity ◽

Thalamic Nuclei ◽

Frequency Burst ◽

Deep Brain

AbstractHigh-frequency peripheral nerve stimulation has emerged as a noninvasive alternative to thalamic deep brain stimulation for some patients with essential tremor. It is not known whether such techniques might be effective for movement disorders in children, nor is the mechanism and transmission of the peripheral stimuli to central brain structures understood. This study was designed to investigate the fidelity of transmission from peripheral nerves to thalamic nuclei in children with dystonia undergoing deep brain stimulation surgery. The ventralis intermediate (VIM) thalamus nuclei showed a robust evoked response to peripheral high-frequency burst stimulation, with a greatest response magnitude to intra-burst frequencies between 50 and 100 Hz, and reliable but smaller responses up to 170 Hz. The earliest response occurred at 12–15 ms following stimulation onset, suggesting rapid high-fidelity transmission between peripheral nerve and thalamic nuclei. A high-bandwidth, low-latency transmission path from peripheral nerve to VIM thalamus is consistent with the importance of rapid and accurate sensory information for the control of coordination and movement via the cerebello-thalamo-cortical pathway. Our results suggest the possibility of non-invasive modulation of thalamic activity in children with dystonia, and therefore the possibility that a subset of children could have beneficial clinical response without the need for invasive deep brain stimulation.

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