Therapeutic Window of Deep Brain Stimulation Using Cathodic Monopolar, Bipolar, Semi‐Bipolar, and Anodic Stimulation

Deep brain stimulation (DBS) is an approved therapy for the treatment of medically refractory and severe movement disorders. However, most existing neurostimulators can only apply continuous stimulation [open-loop DBS (OL-DBS)], ignoring patient behavior and environmental factors, which consequently leads to an inefficient therapy, thus limiting the therapeutic window. Here, we established the feasibility of a self-adjusting therapeutic DBS [closed-loop DBS (CL-DBS)], fully embedded in a chronic investigational neurostimulator (Activa PC + S), for three patients affected by essential tremor (ET) enrolled in a longitudinal (6 months) within-subject crossover protocol (DBS OFF, OL-DBS, and CL-DBS). Most patients with ET experience involuntary limb tremor during goal-directed movements, but not during rest. Hence, the proposed CL-DBS paradigm explored the efficacy of modulating the stimulation amplitude based on patient-specific motor behavior, suppressing the pathological tremor on-demand based on a cortical electrode detecting upper limb motor activity. Here, we demonstrated how the proposed stimulation paradigm was able to achieve clinical efficacy and tremor suppression comparable with OL-DBS in a range of movements (cup reaching, proximal and distal posture, water pouring, and writing) while having a consistent reduction in energy delivery. The proposed paradigm is an important step toward a behaviorally modulated fully embedded DBS system, capable of delivering stimulation only when needed, and potentially mitigating pitfalls of OL-DBS, such as DBS-induced side effects and premature device replacement.

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Expanding the Therapeutic Window of Deep Brain Stimulation in Parkinson's Disease by Means of Directional Leads

Case Medical Research ◽

10.31525/ct1-nct04093544 ◽

2019 ◽

Author(s):

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Brain Stimulation ◽

Therapeutic Window ◽

Deep Brain

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Comparison of methodologies for modeling directional deep brain stimulation electrodes

PLoS ONE ◽

10.1371/journal.pone.0260162 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0260162

Author(s):

Anneke M. Frankemolle-Gilbert ◽

Bryan Howell ◽

Kelsey L. Bower ◽

Peter H. Veltink ◽

Tjitske Heida ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Computational Models ◽

Current Source ◽

Therapeutic Window ◽

Voltage Distribution ◽

Model Variant ◽

Electrode Contact ◽

The Brain ◽

Deep Brain

Deep brain stimulation (DBS) is an established clinical therapy, and directional DBS electrode designs are now commonly used in clinical practice. Directional DBS leads have the ability to increase the therapeutic window of stimulation, but they also increase the complexity of clinical programming. Therefore, computational models of DBS have become available in clinical software tools that are designed to assist in the identification of therapeutic settings. However, the details of how the DBS model is implemented can influence the predictions of the software. The goal of this study was to compare different methods for representing directional DBS electrodes within finite element volume conductor (VC) models. We evaluated 15 different DBS VC model variants and quantified how their differences influenced estimates on the spatial extent of axonal activation from DBS. Each DBS VC model included the same representation of the brain and head, but the details of the current source and electrode contact were different for each model variant. The more complex VC models explicitly represented the DBS electrode contacts, while the more simple VC models used boundary condition approximations. The more complex VC models required 2–3 times longer to mesh, build, and solve for the DBS voltage distribution than the more simple VC models. Differences in individual axonal activation thresholds across the VC model variants were substantial (-24% to +47%). However, when comparing total activation of an axon population, or estimates of an activation volume, the differences between model variants decreased (-7% to +8%). Nonetheless, the technical details of how the electrode contact and current source are represented in the DBS VC model can directly affect estimates of the voltage distribution and electric field in the brain tissue.

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Walking Speed Reliably Measures Clinically Significant Changes in Gait by Directional Deep Brain Stimulation

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2020.618366 ◽

2021 ◽

Vol 14 ◽

Author(s):

Christopher P. Hurt ◽

Daniel J. Kuhman ◽

Barton L. Guthrie ◽

Carla R. Lima ◽

Melissa Wade ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Walking Speed ◽

Step Length ◽

Therapeutic Window ◽

Significant Difference ◽

Gait Dysfunction ◽

Clinically Significant ◽

Deep Brain

Introduction: Although deep brain stimulation (DBS) often improves levodopa-responsive gait symptoms, robust therapies for gait dysfunction from Parkinson's disease (PD) remain a major unmet need. Walking speed could represent a simple, integrated tool to assess DBS efficacy but is often not examined systematically or quantitatively during DBS programming. Here we investigate the reliability and functional significance of changes in gait by directional DBS in the subthalamic nucleus.Methods: Nineteen patients underwent unilateral subthalamic nucleus DBS surgery with an eight-contact directional lead (1-3-3-1 configuration) in the most severely affected hemisphere. They arrived off dopaminergic medications >12 h preoperatively and for device activation 1 month after surgery. We measured a comfortable walking speed using an instrumented walkway with DBS off and at each of 10 stimulation configurations (six directional contacts, two virtual rings, and two circular rings) at the midpoint of the therapeutic window. Repeated measures of ANOVA contrasted preoperative vs. maximum and minimum walking speeds across DBS configurations during device activation. Intraclass correlation coefficients examined walking speed reliability across the four trials within each DBS configuration. We also investigated whether changes in walking speed related to modification of step length vs. cadence with a one-sample t-test.Results: Mean comfortable walking speed improved significantly with DBS on vs. both DBS off and minimum speeds with DBS on (p < 0.001, respectively). Pairwise comparisons showed no significant difference between DBS off and minimum comfortable walking speed with DBS on (p = 1.000). Intraclass correlations were ≥0.949 within each condition. Changes in comfortable walk speed were conferred primarily by changes in step length (p < 0.004).Conclusion: Acute assessment of walking speed is a reliable, clinically meaningful measure of gait function during DBS activation. Directional and circular unilateral subthalamic DBS in appropriate configurations elicit acute and clinically significant improvements in gait dysfunction related to PD. Next-generation directional DBS technologies have significant potential to enhance gait by individually tailoring stimulation parameters to optimize efficacy.

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Less is more – Pulse width dependent therapeutic window in deep brain stimulation for essential tremor

Brain Stimulation ◽

10.1016/j.brs.2018.04.019 ◽

2018 ◽

Vol 11 (5) ◽

pp. 1132-1139 ◽

Cited By ~ 14

Author(s):

Alexia-Sabine Moldovan ◽

Christian Johannes Hartmann ◽

Carlos Trenado ◽

Nicola Meumertzheim ◽

Philipp Jörg Slotty ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Essential Tremor ◽

Brain Stimulation ◽

Pulse Width ◽

Therapeutic Window ◽

Less Is More ◽

Deep Brain

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Selection of deep brain stimulation contacts using volume of tissue activated software following subthalamic nucleus stimulation

Journal of Neurosurgery ◽

10.3171/2020.6.jns192157 ◽

2020 ◽

pp. 1-8

Author(s):

Mathilde Devaluez ◽

Melissa Tir ◽

Pierre Krystkowiak ◽

Mickael Aubignat ◽

Michel Lefranc

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Subthalamic Nucleus ◽

Clinical Data ◽

Brain Stimulation ◽

Therapeutic Window ◽

Patient Specific ◽

Subthalamic Nucleus Stimulation ◽

Deep Brain

OBJECTIVEHigh-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in the treatment of motor symptoms of Parkinson’s disease. Using a patient-specific lead and volume of tissue activated (VTA) software, it is possible to visualize contact positions in the context of the patient’s own anatomy. In this study, the authors’ aim was to demonstrate that VTA software can be used in clinical practice to help determine the clinical effectiveness of stimulation in patients with Parkinson’s disease undergoing DBS of the STN.METHODSBrain images of 26 patients undergoing STN DBS were analyzed using VTA software. Preoperative clinical and neuropsychological data were collected. Contacts were chosen by two experts in DBS blinded to the clinical data. A therapeutic window of amplitude was determined. These results were compared with the parameter settings for each patient. Data were obtained at 3 months and 1 year postsurgery.RESULTSIn 90.4% (95% CI 82%–98%) of the patients, the contacts identified by the VTA software were concordant with the clinically effective contacts or with an effective contact in contact-by-contact testing. The therapeutic window of amplitude selected virtually included 81.3% of the clinical amplitudes.CONCLUSIONSVTA software appears to present significant concordance with clinical data for selecting contacts and stimulation parameters that could help in postoperative follow-up and programming.

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Data-Driven Prediction of the Therapeutic Window during Subthalamic Deep Brain Stimulation Surgery

Stereotactic and Functional Neurosurgery ◽

10.1159/000488683 ◽

2018 ◽

Vol 96 (3) ◽

pp. 142-150

Author(s):

Clément Baumgarten ◽

Claire Haegelen ◽

Yulong Zhao ◽

Paul Sauleau ◽

Pierre Jannin

Keyword(s):

Deep Brain Stimulation ◽

Brain Stimulation ◽

Data Driven ◽

Therapeutic Window ◽

Deep Brain Stimulation Surgery ◽

Deep Brain

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Short Pulse and Conventional Deep Brain Stimulation Equally Improve the Parkinsonian Gait Disorder

Journal of Parkinson s Disease ◽

10.3233/jpd-202492 ◽

2021 ◽

pp. 1-10

Author(s):

Aline Seger ◽

Alessandro Gulberti ◽

Eik Vettorazzi ◽

Hanna Braa ◽

Carsten Buhmann ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Gait Analysis ◽

Brain Stimulation ◽

Pulse Width ◽

Short Pulse ◽

Therapeutic Window ◽

Gait Velocity ◽

Secondary Endpoints ◽

Quantitative Gait Analysis ◽

Deep Brain

Background: Gait disturbances and balance remain challenging issues in Parkinsonian patients (PD) with deep brain stimulation (DBS). Short pulse deep brain stimulation (spDBS) increases the therapeutic window in PD patients, yet the effect on gait and postural symptoms remains unknown. Objective: We assessed the efficacy of spDBS compared to conventional DBS (cDBS) within the subthalamic nucleus (STN) on Parkinsonian gait. Methods: The study was a single-centre, randomized, double-blind, clinical short-term trial. 20 PD patients were studied postoperatively in three different conditions (DBS stimulation switched off (off DBS), spDBS with 40μs pulse width, cDBS with 60μs pulse width) on regular medication. The primary endpoint was the relative difference of gait velocity at self-paced speed during quantitative gait analysis between stimulation conditions. Secondary endpoints were changes of further measures of quantitative gait analysis, Ziegler course, Berg balance scale, FOG questionnaire, MDS-UPDRS, PDQ-39, and HADS. Mixed-model analysis and post-hoc t-tests were performed. Results: Both spDBS and cDBS improved gait velocity at self-paced speed compared to off DBS, however, there was no significant difference between both stimulation modes. Still, nearly half of the patients preferred spDBS over cDBS subjectively. Both stimulation modes were equally effective in improving secondary endpoints of gait, balance, motor and non-motor performances. Conclusion: The use of spDBS and cDBS is equally effective in improving gait and balance in PD and might be beneficial in specified cohorts of PD patients.

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