Optimal Parameters of Deep Brain Stimulation in Essential Tremor: A Meta-Analysis and Novel Programming Strategy

The programming of deep brain stimulation (DBS) parameters for tremor is laborious and empirical. Despite extensive efforts, the end-result is often suboptimal. One reason for this is the poorly understood relationship between the stimulation parameters’ voltage, pulse width, and frequency. In this study, we aim to improve DBS programming for essential tremor (ET) by exploring a new strategy. At first, the role of the individual DBS parameters in tremor control was characterized using a meta-analysis documenting all the available parameters and tremor outcomes. In our novel programming strategy, we applied 10 random combinations of stimulation parameters in eight ET-DBS patients with suboptimal tremor control. Tremor severity was assessed using accelerometers and immediate and sustained patient-reported outcomes (PRO’s), including the occurrence of side-effects. The meta-analysis showed no substantial relationship between individual DBS parameters and tremor suppression. Nevertheless, with our novel programming strategy, a significantly improved (accelerometer p = 0.02, PRO p = 0.02) and sustained (p = 0.01) tremor suppression compared to baseline was achieved. Less side-effects were encountered compared to baseline. Our pilot data show that with this novel approach, tremor control can be improved in ET patients with suboptimal tremor control on DBS. In addition, this approach proved to have a beneficial effect on stimulation-related complications.

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Shorter pulse width reduces gait disturbances following deep brain stimulation for essential tremor

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-319427 ◽

2019 ◽

Vol 90 (9) ◽

pp. 1046-1050 ◽

Cited By ~ 7

Author(s):

Daniel Kroneberg ◽

Siobhan Ewert ◽

Anne-Christiane Meyer ◽

Andrea A Kühn

Keyword(s):

Deep Brain Stimulation ◽

Side Effects ◽

Essential Tremor ◽

Brain Stimulation ◽

Pulse Width ◽

Stride Length ◽

Gait Parameters ◽

Tremor Suppression ◽

Gait Disturbances ◽

Deep Brain

ObjectiveGait disturbances are frequent side effects occurring during chronic thalamic deep brain stimulation (DBS) in patients with essential tremor (ET). Adapting stimulation settings to shorter pulse widths has been shown to reduce side effects of subthalamic DBS. Here, we assess how a reduction of pulse width changes gait performance of affected patients.MethodsSensor-based gait assessment was performed to record spatiotemporal gait parameters in 10 healthy subjects (HS) and 7 patients with ET with gait disturbances following thalamic DBS. Patients were tested during standard DBS, after 72 hours of stimulation withdrawal and at least 30 days after adjusting DBS settings to a shorter pulse width of 40 µs (DBS40PW).ResultsPatients with ET on standard DBS showed significantly higher variability of several spatiotemporal gait parameters compared with HS. Variability of stride length and range of motion of the shanks significantly decreased OFF DBS as compared with standard DBS. This improvement was maintained over 30 days with DBS40PW while providing effective tremor suppression in six out of seven patients.ConclusionShorter pulse widths may reduce gait disturbances in patients with ET that are induced by DBS while preserving a level of tremor suppression equal to standard stimulation settings.

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Thalamic Deep Brain Stimulation in Essential Tremor Plus Is as Effective as in Essential Tremor

Brain Sciences ◽

10.3390/brainsci10120970 ◽

2020 ◽

Vol 10 (12) ◽

pp. 970

Author(s):

Julia K. Steffen ◽

Hannah Jergas ◽

Jan N. Petry-Schmelzer ◽

Till A. Dembek ◽

Tabea Thies ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Essential Tremor ◽

Brain Stimulation ◽

Rating Scale ◽

Action Tremor ◽

Active Electrode ◽

Neurological Signs ◽

Stimulation Parameters ◽

Tremor Suppression ◽

Deep Brain

The new essential tremor (ET) classification defined ET-plus (ET-p) as an ET subgroup with additional neurological signs besides action tremor. While deep brain stimulation (DBS) is effective in ET, there are no studies specifically addressing DBS effects in ET-p. 44 patients with medication-refractory ET and thalamic/subthalamic DBS implanted at our center were postoperatively classified into ET and ET-p according to preoperative documentation. Tremor suppression with DBS (stimulation ON vs. preoperative baseline and vs. stimulation OFF), measured via the Fahn–Tolosa–Marin tremor rating scale (TRS), stimulation parameters, and the location of active contacts were compared between patients classified as ET and ET-p. TRS scores at baseline were higher in ET-p. ET-p patients showed comparable tremor reduction as patients with ET, albeit higher stimulation parameters were needed in ET-p. Active electrode contacts were located more dorsally in ET-p of uncertain reason. Our data show that DBS is similarly effective in ET-p compared to ET. TRS scores were higher in ET-p preoperatively, and higher stimulation parameters were needed for tremor reduction compared to ET. The latter may be related to a more dorsal location of active electrode contacts in the ET-p group of this cohort. Prospective studies are warranted to investigate DBS in ET-p further.

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Gait worsening and the microlesion effect following deep brain stimulation for essential tremor

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-319723 ◽

2019 ◽

Vol 90 (8) ◽

pp. 913-919 ◽

Cited By ~ 2

Author(s):

Ryan Roemmich ◽

Jaimie A Roper ◽

Robert S Eisinger ◽

Jackson N Cagle ◽

Lauren Maine ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Essential Tremor ◽

Brain Stimulation ◽

Repeated Measures ◽

Walking Speed ◽

Stimulation Parameters ◽

Gait Parameters ◽

Before And After ◽

Walking Speeds ◽

Deep Brain

ObjectiveTo investigate the effects of unilateral thalamic deep brain stimulation (DBS) on walking in persons with medication-refractory essential tremor (ET).MethodsWe performed laboratory-based gait analyses on 24 persons with medication-refractory ET before and after unilateral thalamic DBS implantation. Normal and tandem walking parameters were analysed across sessions (PRE-DBS/DBS OFF/DBS ON) by repeated measures analyses of variance. Pearson’s correlations assessed whether changes in walking after DBS were global (ie, related across gait parameters). Baseline characteristics, lead locations and stimulation parameters were analysed as possible contributors to gait effects.ResultsDBS minimally affected gait at the cohort level. However, 25% of participants experienced clinically meaningful gait worsening. Walking speed decreased by >30% in two participants and by >10% in four others. Decreased walking speed correlated with increased gait variability, indicating global gait worsening in affected participants. The worsening persisted even after the stimulation was turned off. Participants with worse baseline tandem walking performance may be more likely to experience post-DBS gait worsening; the percentage of tandem missteps at baseline was nearly three times higher and tandem walking speeds were approximately 30% slower in participants who experienced gait worsening. However, these differences in tandem walking in persons with gait worsening as compared with those without worsening were not statistically significant. Lead locations and stimulation parameters were similar in participants with and without gait worsening.ConclusionGlobal gait worsening occurred in 25% of participants with unilateral DBS for medication-refractory ET. The effect was present on and off stimulation, likely indicating a microlesion effect.

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Awake versus asleep deep brain stimulation for Parkinson’s disease: a critical comparison and meta-analysis

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2016-314500 ◽

2017 ◽

Vol 89 (7) ◽

pp. 687-691 ◽

Cited By ~ 35

Author(s):

Allen L Ho ◽

Rohaid Ali ◽

Ian D Connolly ◽

Jaimie M Henderson ◽

Rohit Dhall ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Deep Brain Stimulation ◽

Side Effects ◽

General Anaesthesia ◽

Brain Stimulation ◽

Meta Analysis ◽

Complication Rates ◽

Significant Difference ◽

Deep Brain

ObjectiveNo definitive comparative studies of the efficacy of ‘awake’ deep brain stimulation (DBS) for Parkinson’s disease (PD) under local or general anaesthesia exist, and there remains significant debate within the field regarding differences in outcomes between these two techniques.MethodsWe conducted a literature review and meta-analysis of all published DBS for PD studies (n=2563) on PubMed from January 2004 to November 2015. Inclusion criteria included patient number >15, report of precision and/or clinical outcomes data, and at least 6 months of follow-up. There were 145 studies, 16 of which were under general anaesthesia. Data were pooled using an inverse-variance weighted, random effects meta-analytic model for observational data.ResultsThere was no significant difference in mean target error between local and general anaesthesia, but there was a significantly less mean number of DBS lead passes with general anaesthesia (p=0.006). There were also significant decreases in DBS complications, with fewer intracerebral haemorrhages and infections with general anaesthesia (p<0.001). There were no significant differences in Unified Parkinson’s Disease Rating Scale (UPDRS) Section II scores off medication, UPDRS III scores off and on medication or levodopa equivalent doses between the two techniques. Awake DBS cohorts had a significantly greater decrease in treatment-related side effects as measured by the UPDRS IV off medication score (78.4% awake vs 59.7% asleep, p=0.022).ConclusionsOur meta-analysis demonstrates that while DBS under general anaesthesia may lead to lower complication rates overall, awake DBS may lead to less treatment-induced side effects. Nevertheless, there were no significant differences in clinical motor outcomes between the two techniques. Thus, DBS under general anaesthesia can be considered at experienced centres in patients who are not candidates for traditional awake DBS or prefer the asleep alternative.

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Modeling mechanisms of tremor reduction for essential tremor using symmetric biphasic DBS

10.1101/585117 ◽

2019 ◽

Cited By ~ 1

Author(s):

Shane Lee ◽

Wael F Asaad ◽

Stephanie R Jones

Keyword(s):

Deep Brain Stimulation ◽

Side Effects ◽

Movement Disorder ◽

Essential Tremor ◽

Brain Stimulation ◽

Future Studies ◽

Tremor Frequency ◽

Ventral Intermediate Nucleus ◽

Different Shapes ◽

Deep Brain

AbstractEssential tremor (ET) is the most common movement disorder, in which the primary symptom is a prominent, involuntary 4–10 Hz movement. For severe, medication refractory cases, deep brain stimulation (DBS) targeting the ventral intermediate nucleus of the thalamus (VIM) can be an effective treatment for cessation of tremor and is thought to work in part by disrupting tremor frequency oscillations (TFOs) in VIM. However, DBS is not universally effective and may be further disrupting cerebellar-mediated activity in the VIM. Here, we applied biophysically detailed computational modeling to investigate whether the efficacy of DBS is affected by the mechanism of generation of TFOs or by the pattern of stimulation. We simulated the effects of DBS using standard, asymmetric pulses as well as biphasic, symmetric pulses to understand biophysical mechanisms of how DBS disrupts TFOs generated either extrinsically or intrinsically. The model results suggested that the efficacy of DBS in the VIM is affected by the mechanism of generation of TFOs. Symmetric biphasic DBS reduced TFOs more than standard DBS in both networks, and these effects were stronger in the intrinsic network. For intrinsic tremor frequency activity, symmetric biphasic DBS was more effective at reducing TFOs. Simulated non-tremor signals were also transmitted during symmetric biphasic DBS, suggesting that this type of DBS may help to reduce side effects caused by disruption of the cerebellothalamocortical pathway. Biophysical details in the model provided a mechanistic interpretation of the cellular and network dynamics contributing to these effects that can be empirically tested in future studies.Significance StatementEssential tremor (ET) is a common movement disorder, whose primary symptom is an involuntary rhythmic movement of the limbs or head. An area of the human tha-lamus demonstrates electrical activity that oscillates at the frequencies of tremor, and deep brain stimulation (DBS) in this area can reduce tremor. It is not fully understood how DBS affects tremor frequency activity in the thalamus, and studying different patterns of DBS stimulation may help to clarify these mechanisms. We created a computational model of different shapes of DBS and studied how they reduce different hypothesized generators of tremor frequency activity. A greater understanding of how DBS affects the thalamus may lead to improved treatments to reduce tremor and alleviate side effects in patients with ET.

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Long-term Thalamic Deep Brain Stimulation for Essential Tremor: Clinical Outcome and Stimulation Parameters

Movement Disorders Clinical Practice ◽

10.1002/mdc3.12337 ◽

2016 ◽

Vol 3 (6) ◽

pp. 567-572 ◽

Cited By ~ 15

Author(s):

Pedro M. Rodríguez Cruz ◽

Antonio Vargas ◽

Carlos Fernández-Carballal ◽

Jose Garbizu ◽

Beatriz De La Casa-Fages ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Clinical Outcome ◽

Essential Tremor ◽

Brain Stimulation ◽

Stimulation Parameters ◽

Deep Brain

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Improved Outcome on Interleaved Deep Brain Stimulation Settings

Deep Brain Stimulation ◽

10.1093/med/9780190647209.003.0032 ◽

2020 ◽

pp. 155-160

Author(s):

Svjetlana Miocinovic ◽

Pravin Khemani ◽

Rebecca Whiddon ◽

Shilpa Chitnis

Keyword(s):

Deep Brain Stimulation ◽

Side Effects ◽

Parkinson Disease ◽

Subthalamic Nucleus ◽

Brain Stimulation ◽

Programming Method ◽

Additional Advantage ◽

Stimulation Parameters ◽

Improved Outcome ◽

Deep Brain

Interleaving is a DBS programming method whereby two sets of stimulation parameters are applied interchangeably (on a millisecond level). This chapter describes a patient with Parkinson disease who was implanted with subthalamic nucleus deep brain stimulation but achieved suboptimal tremor control with conventional programming (monopolar, double monopolar, or bipolar settings). Interleaving allowed the dorsal contact to be set to a higher setting, while the contact below was set to a tolerable lower setting. Together, the two contacts provided complete tremor resolution without side effects. It is unknown whether interleaving provides any additional advantage over simply allowing use of different amplitudes at different contacts, but potential mechanisms are discussed.

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Long-term results of thalamic deep brain stimulation for essential tremor

Journal of Neurosurgery ◽

10.3171/2009.10.jns09371 ◽

2010 ◽

Vol 112 (6) ◽

pp. 1271-1276 ◽

Cited By ~ 119

Author(s):

Kai Zhang ◽

Sanjay Bhatia ◽

Michael Y. Oh ◽

David Cohen ◽

Cindy Angle ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Essential Tremor ◽

Visual Analog Scale ◽

Brain Stimulation ◽

Analog Scale ◽

Stimulation Parameters ◽

Long Term Follow Up ◽

Deep Brain

Object Deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus (VIM) has proven to be efficacious in the treatment of essential tremor (ET). The authors report on long-term follow-up of a series of patients treated at 1 institution by 1 neurosurgeon. Methods Thirty-four patients with ET received unilateral or bilateral VIM DBS. The tremor and handwriting components of the Fahn-Tolosa-Marin clinical tremor rating scale were assessed pre- and postoperatively. Visual analog scale scores for overall patient satisfaction and tremor control were recorded. Stimulation parameters at different intervals after surgery were also recorded. Results The average follow-up period was 56.9 months. The average tremor score improved from 3.27 preoperatively to 0.64 postoperatively (on stimulation; p < 0.001) and the average handwriting score improved from 2.94 to 0.89 (p < 0.001). The average visual analog scale score for overall satisfaction was 8.12 and for tremor control was 1.43. Overall, there was an 80.4% improvement in tremor and 69.7% improvement in handwriting. In 12 patients both tremor and handwriting scores were compared between 57.3 months and 90.7 months after surgery and no significant changes were discovered. Comparison of stimulation parameters at onset and at 1–3, 3–5, 5–7, and > 7 years after surgery showed significant differences, with a gradual increase in stimulation parameters within 5 years after surgery. The overall hardware-related complication rate was 23.5%. Conclusions Deep brain stimulation of the VIM is an efficient and safe treatment for ET. Tremor and handwriting improvements in long-term follow-up are stable. The patients' perception of their outcome is quite good. However, tolerance may develop in some patients requiring changes in stimulation parameters.

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Deep Brain Stimulation Effects on Olfactory Dysfunction of Parkinson’s Disease - A Meta-Analysis

10.21203/rs.3.rs-33501/v1 ◽

2020 ◽

Author(s):

Chao Li ◽

Xue-lian Chu ◽

Min Tian ◽

Feng Li ◽

Shu-jun Xu ◽

...

Keyword(s):

Deep Brain Stimulation ◽

Publication Bias ◽

Therapeutic Effect ◽

Brain Stimulation ◽

Early Stage ◽

Meta Analysis ◽

Olfactory Function ◽

Efficient Treatment ◽

Stimulation Parameters ◽

Deep Brain

Abstract Background: Non-motor symptoms in PD usually arise at very early stage and suffer the damage decades from diagnose. Deep brain stimulation (DBS) is considered as a highly efficient treatment option for PD’s motor function. However, the effect of DBS on NMS, especially hyposmia, has not been fully understood and there are contradictory data among different researches.Objective: The objective of this study was to evaluate the therapeutic effect of DBS on hyposmia in PD patients with a cohort study and identified whether the olfactory function scores influence the final surgery effect.Methods: A meta-analysis including six studies with 326 patients were conducted to evaluate the exact therapeutic effect of DBS on hyposmia in PD. Sub-group analyses based on sample size, gender, stimulation parameters were carried out to distinguish the difference. Sensitivity analysis was conducted to evaluate studies’ heterogeneity and stability. Potential publication bias were evaluated by Egger’s tests and the funnel plots.Results: Our study showed that DBS had clearly improved olfactory function in Parkinson patients (P < 0.0001) and the group heterogeneity as well as the publication bias advocate the convince of the result (Heterogeneity: Chi² = 6.39, df = 5 (P = 0.38); I² = 22%). Subgroup analysis also found that different groups of gender, education level or stimulation parameters have no obvious discrepancy on olfactory function improvement except age groups.Conclusion: In summary, this article summarize studies about DBS and hyposmia and offer evidences for the notion that DBS has authentic therapeutic value on the hyposmia in PD.

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