Ventral Intermediate Nucleus Research Articles

Endovascular deep brain stimulation: Investigating the relationship between vascular structures and deep brain stimulation targets

BackgroundEndovascular delivery of current using ‘stentrodes’ – electrode bearing stents – constitutes a potential alternative to conventional deep brain stimulation (DBS). The precise neuroanatomical relationships between DBS targets and the vascular system, however, are poorly characterized to date. ObjectiveTo establish the relationships between cerebrovascular system and DBS targets and investigate the feasibility of endovascular stimulation as an alternative to DBS. MethodsNeuroanatomical targets as employed during deep brain stimulation (anterior limb of the internal capsule, dentatorubrothalamic tract, fornix, globus pallidus pars interna, medial forebrain bundle, nucleus accumbens, pedunculopontine nucleus, subcallosal cingulate cortex, subthalamic nucleus, and ventral intermediate nucleus) were superimposed onto probabilistic vascular atlases obtained from 42 healthy individuals. Euclidian distances between targets and associated vessels were measured. To determine the electrical currents necessary to encapsulate the predefined neurosurgical targets and identify potentially side-effect inducing substrates, a preliminary volume of tissue activated (VTA) analysis was performed. ResultsSix out of ten DBS targets were deemed suitable for endovascular stimulation: medial forebrain bundle (vascular site: P1 segment of posterior cerebral artery), nucleus accumbens (vascular site: A1 segment of anterior cerebral artery), dentatorubrothalamic tract (vascular site: s2 segment of superior cerebellar artery), fornix (vascular site: internal cerebral vein), pedunculopontine nucleus (vascular site: lateral mesencephalic vein), and subcallosal cingulate cortex (vascular site: A2 segment of anterior cerebral artery). While VTAs effectively encapsulated mfb and NA at current thresholds of 3.5 V and 4.5 V respectively, incremental amplitude increases were required to effectively cover fornix, PPN and SCC target (mean voltage: 8.2 ± 4.8 V, range: 3.0–17.0 V). The side-effect profile associated with endovascular stimulation seems to be comparable to conventional lead implantation. Tailoring of targets towards vascular sites, however, may allow to reduce adverse effects, while maintaining the efficacy of neural entrainment within the target tissue. ConclusionsWhile several challenges remain at present, endovascular stimulation of select DBS targets seems feasible offering novel and exciting opportunities in the neuromodulation armamentarium.

Fully implanted adaptive deep brain stimulation in freely moving essential tremor patients

Objective. Deep brain stimulation (DBS) is a safe and established treatment for essential tremor (ET) and several other movement disorders. One approach to improving DBS therapy is adaptive DBS (aDBS), in which stimulation parameters are modulated in real time based on biofeedback from either external or implanted sensors. Previously tested systems have fallen short of translational applicability due to the requirement for patients to continuously wear the necessary sensors or processing devices, as well as privacy and security concerns. Approach. We designed and implemented a translation-ready training data collection system for fully implanted aDBS. Two patients chronically implanted with electrocorticography strips over the hand portion of M1 and DBS probes in the ipsilateral ventral intermediate nucleus of the thalamus for treatment of ET were recruited for this study. Training was conducted using a translation-ready distributed training procedure, allowing a substantially higher degree of control over data collection than previous works. A linear classifier was trained using this system, biased towards activating stimulation in accordance with clinical considerations. Main results. The clinically relevant average false negative rate, defined as fraction of time during which stimulation dropped below clinical levels during movement epochs, was 0.036. Tremor suppression, calculated through analysis of gyroscope data, was 33.2% more effective on average with aDBS than with continuous DBS. During a period of free movement with aDBS, one patient reported a slight paresthesia; patients noticed no difference in treatment efficacy between systems. Significance. Here is presented the first translation-ready training procedure for a fully embedded aDBS control system for MDs and one of the first examples of such a system in ET, adding to the consensus that fully implanted aDBS systems are sufficiently mature for broader deployment in treatment of movement disorders.

Ataxia and tolerance after thalamic deep brain stimulation for essential tremor

BackgroundDeep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) thalamus is highly effective to treat medication-refractory essential tremor (ET). Complications of stimulation-induced ataxia and tolerance have been reported in limited series, ranging from 5 to 40%. ObjectiveWe analyzed a large single-center cohort of ET patients treated with thalamic DBS to assess rates of ataxia and tolerance. MethodsRetrospective study of all ET patients that underwent VIM DBS at Mayo Clinic from 2010 to 2014. Demographic, clinical and DBS data were extracted. Risk factors, complications and time to onset of tolerance and ataxia were examined. ResultsOne hundred and thirteen ET patients (51% male) of mean age 68 ± 10 years and mean ET duration 27 ± 18 years underwent DBS during the study period. Of these, 98 (87%) had follow-up of ≥6 months (mean 4.0 ± 1.5 years) and were included for analysis. Complications of isolated ataxia (26%), isolated tolerance (4%), both tolerance and ataxia (9%), or neither (61%) were identified. Development of ataxia was about 3 times more common than tolerance (35% vs. 13%). The mean time to ataxia was 5.5 ± 0.3 years postoperatively. Risk factors for ataxia were baseline ataxic features, older age, and shorter ET disease duration. Small sample size limited calculation of risk factors and onset time for tolerance. ConclusionsStimulation-related ataxia occurred in one-third of ET patients, while tolerance was less common. Presence of baseline ataxia, age, and disease duration may aid counseling of stimulation-related ataxia risk. Larger studies are warranted to confirm these findings and further assess risk factors for tolerance.

Radiocirugía estereotáctica con Gamma Knife® como tratamiento del temblor esencial y parkinsoniano: experiencia a largo plazo

IntroductionUnilateral Gamma Knife™ stereotactic radiosurgery on the ventral-intermediate nucleus of the thalamus is a minimally invasive neurosurgical option for refractory tremor. We describe the experience of Gamma Knife™ thalamotomy (GKT) in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) at our specialised stereotactic neurosurgery unit. MethodsWe reviewed the cases of patients treated with GKT between January 2014 and February 2018 with a minimum of 12 months’ follow-up. We analysed clinical and demographic variables, indication, radiation dose, effectiveness (based on subscales of the Fahn-Tolosa-Marin [FTM] scale and the Movement Disorders Society-Unified Parkinson's Disease Rating Scale [MDS-UPDRS] motor score), and adverse events. ResultsThirteen patients were registered, 6 with a diagnosis of tremor-dominant PD, four with refractory ET, and three with ET and PD. Median age was 78 years (range, 62-83), with seven patients aged over 75 years. Four patients were receiving anticoagulants and two had history of stroke. The maximum radiation dose administered was 130 Gy. Mean (standard deviation) follow-up duration was 30.0 (14.5) months. Significant tremor improvement was observed on the FTM subscales: 63.6% at 12 months and 63.5% at the end of follow-up; MDS-UPDRS tremor items showed improvements of 71.3% at 12 months and 60.3% at the end of follow up. Eleven patients reported significant improvements in quality of life, and 3 reported mild and transient adverse effects. ConclusionsThis is the largest series of patients with essential and parkinsonian tremor treated with GKT and followed up in the long term in Spain. GKT can be safe and effective in the long term in patients with refractory tremor, including in elderly patients and those receiving anticoagulants.

Comparing Programming Sessions of Vim-DBS.

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.

Case report of hyperacute edema and cavitation following deep brain stimulation lead implantation

Background: Postoperative cerebral edema around a deep brain stimulation (DBS) electrode is an uncommonly reported complication of DBS surgery. The etiology of this remains unknown, and the presentation is highly variable; however, the patients generally report a good outcome.Case Description: Here, we report an unusual presentation of postoperative edema in a 66-year-old female who has bilateral dentatorubrothalamic tract (specifically, the ventral intermediate nucleus) DBS for a mixed type tremor disorder. Initial postoperative computed tomography (CT) was unremarkable and the patient was admitted for observation. She declined later on postoperative day (POD) 1 and became lethargic. Stat head CT scan performed revealed marked left-sided peri-lead edema extending into the centrum semiovale with cystic cavitation, and trace right-sided edema. On POD 2, the patient was alert, but with global aphasia, right-sided neglect, and a plegic right upper extremity. Corticosteroids were started and a complete infectious workup was unremarkable. She was intubated and ultimately required a tracheostomy and percutaneous gastrostomy tube. She returned to the clinic 3 months postoperatively completely recovered and ready for battery implantation.Conclusion: While this is an unusual presentation of cerebral edema following DBS placement, ultimately, the outcome was good similar to other reported cases. Supportive care and corticosteroids remain the treatment of choice for this phenomenon.

A-096 Reliable Change Indices as a Measure of Neurocognitive Change following Deep Brain Stimulation for Essential Tremor

Abstract Objective Deep brain stimulation (DBS) is a widely used treatment for essential tremor (ET). To assess for neurocognitive decline following DBS, most studies use statistical methods that directly compare changes in test scores between pre- and post-surgical evaluations. By contrast, reliable change scores are calculated using regression-based models that account for practice effect and systematic error that can occur between repeat test administrations. We sought to determine the utility of reliable change scores in monitoring neuropsychological function following DBS. Method Twenty-eight ET patients (M age = 70.2 ± 6.3, 57% female) completed neuropsychological evaluations at an outpatient clinic 6.4 ± 3.6 months before and 6.7 ± 1.9 months after DBS placement within the ventral intermediate nucleus of the thalamus (71% left-sided). Wilcoxon signed rank tests were used to identify differences in performance using absolute change versus reliable change scores. Results There were no significant absolute differences between pre- and post-surgery scores on tests of attention, processing speed, executive function, object naming, verbal fluency, or learning and memory. By contrast, significant differences in reliable change scores from zero were identified on tests of phonemic fluency (p < .001), semantic fluency (p = .05), and verbal learning (p = .005). Conclusions Analyses that used reliable change scores identified post-surgical declines that were not evident in traditional statistical comparisons. Results suggest that reliable change indices are useful tools for monitoring changes in neurocognitive functions that can occur following DBS and related neuromodulation treatments.

Improved Vim targeting for focused ultrasound ablation treatment of essential tremor: A probabilistic and patient-specific approach.

Magnetic resonance‐guided focused ultrasound (MRgFUS) ablation of the ventral intermediate (Vim) thalamic nucleus is an incisionless treatment for essential tremor (ET). The standard initial targeting method uses an approximate, atlas‐based stereotactic approach. We developed a new patient‐specific targeting method to identify an individual's Vim and the optimal MRgFUS target region therein for suppression of tremor. In this retrospective study of 14 ET patients treated with MRgFUS, we investigated the ability of WMnMPRAGE, a highly sensitive and robust sequence for imaging gray matter‐white matter contrast, to identify the Vim, FUS ablation, and a clinically efficacious region within the Vim in individual patients. We found that WMnMPRAGE can directly visualize the Vim in ET patients, segmenting this nucleus using manual or automated segmentation capabilities developed by our group. WMnMPRAGE also delineated the ablation's core and penumbra, and showed that all patients' ablation cores lay primarily within their Vim segmentations. We found no significant correlations between standard ablation features (e.g., ablation volume, Vim‐ablation overlap) and 1‐month post‐treatment clinical outcome. We then defined a group‐based probabilistic target, which was nonlinearly warped to individual brains; this target was located within the Vim for all patients. The overlaps between this target and patient ablation cores correlated significantly with 1‐month clinical outcome (r = −.57, p = .03), in contrast to the standard target (r = −.23, p = .44). We conclude that WMnMPRAGE is a highly sensitive sequence for segmenting Vim and ablation boundaries in individual patients, allowing us to find a novel tremor‐associated center within Vim and potentially improving MRgFUS treatment for ET.

Outcomes and Adverse Effects of Deep Brain Stimulation on the Ventral Intermediate Nucleus in Patients with Essential Tremor

Objective This study was aimed at identifying the potential outcome predictors, comparing the efficacy in patients with different tremor characteristics, and summarizing the adverse effect rates (AERs) of deep brain stimulation on the ventral intermediate nucleus (VIM-DBS) for essential tremor (ET). Methods An extensive search of articles published to date in 2019 was conducted, and two main aspects were analyzed. Improvement was calculated as a percentage of change in any objective tremor rating scale (TRS) and analyzed by subgroup analyses of patients' tremor characteristics, laterality, and stimulation parameters. Furthermore, the AERs were analyzed as follows: the adverse effects (AEs) were classified as stimulation-related, surgical-related, or device-related effects. A simple regression analysis was used to identify the potential prognostic factors, and a two-sample mean-comparison test was used to verify the statistical significance of the subgroup analyses. Results Forty-six articles involving 1714 patients were included in the meta-analysis. The pooled improvement in any objective TRS score was 61.3% (95% CI: 0.564-0.660) at the mean follow-up visit (20.0 ± 17.3 months). The midline and extremity symptoms showed consistent improvement (P = 0.440), and the results of the comparison of postural and kinetic tremor were the same (P = 0.219). In addition, the improvement in rest tremor was similar to that in action tremor (OR = 2.759, P = 0.120). In the simple regression analysis, the preoperative Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) scores and follow-up time were negatively correlated with the percentage change in any objective TRS score (P < 0.05). The most common adverse event was dysarthria (10.5%), which is a stimulation-related AE (23.6%), while the rates of the surgical-related and device-related AEs were 6.4% and 11.5%, respectively. Conclusion VIM-DBS is an efficient and safe surgical method in ET, and the efficacy was not affected by the body distribution of tremor, age at surgery, and disease duration. Lower preoperative FTM-TRS scores likely indicate greater improvement, and the effect of VIM-DBS declines over time.

Transcranial Magnetic Resonance-Guided Focused Ultrasound Thalamotomy in Essential Tremor: A Comprehensive Lesion Characterization.

Transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy is a novel and effective treatment for controlling tremor in essential tremor patients. To provide a comprehensive characterization of the radiological, topographical, and volumetric aspects of the tcMRgFUS thalamic lesion, and to quantify how they relate to the clinical outcomes. In this study, clinical and radiological data from forty patients with medically-refractory essential tremor treated with unilateral tcMRgFUS thalamotomy were retrospectively analyzed. Treatment efficacy was assessed with Clinical Rating Scale for Tremor (CRST). Lesions were manually segmented on T1, T2, and susceptibility-weighted images, and 3-dimensional topographical analysis was then carried out. Statistical comparisons were performed using nonparametric statistics. The greatest clinical improvement was correlated with a more inferior and posterior lesion, a bigger lesion volume, and percentage of the ventral intermediate nucleus covered by the lesion; whereas, the largest lesions accounted for the occurrence of gait imbalance. Furthermore, the volume of the lesion was significantly predicted by the number of sonications surpassing 52°C. Here we provide a comprehensive characterization of the thalamic tcMRgFUS lesion including radiological and topographical analysis. Our results indicate that the location and volume of the lesion were significantly associated with the clinical outcome and that mid-temperatures may be responsible for the lesion size. This could serve ultimately to improve targeting and judgment and to optimize clinical outcome of tcMRgFUS thalamotomy.

Vim stereotactic radiosurgical thalamotomy for drug-resistant idiopathic Holmes tremor: a case report

We share our experience with stereotactic gamma knife thalamotomy (GKT) for medically refractory Holmes tremor (HT). A 22-year-old patient underwent gamma knife thalamotomy at ventrointermediate nucleus for disabling HT of the right upper limb. A single 4-mm isocenter was used to target the ventral intermediate nucleus with 130Gy radiation. At 4months follow up, we observed 84% improvement in his Fahn-Tolosa-Marin (FTM) rating scale with significant improvement in the right upper limb dystonic tremor. There was only subtle improvement in the ataxic component of the right lower limb. At 1year after stereotactic GKT, there was sustained neurological improvement with no side effect, We present the stereotactic GKT as a treatment modality for drug-resistant HT. Moreover, it may be considered an alternate treatment modality especially in patients reluctant or contraindicated for any invasive surgical technique. CLINICAL TRIAL REGISTRATION NUMBER: Not required.

Two-year Follow-up Results of Magnetic Resonance Imaging-guided Focused Ultrasound Unilateral Thalamotomy for Medication-refractory Essential Tremor.

Objective To investigate the long-term efficacy and safety of magnetic resonance imaging-guided focused ultrasound (MRgFUS) unilateral ventral intermediate nucleus (Vim) thalamotomy for medication-refractory essential tremor (ET). Methods We performed MRgFUS left-sided Vim thalamotomy for 10 medication-refractory ET patients (8 men and 2 women, aged 67.1±17.5 years, all right-handed). We followed them for 2 years using the clinical rating scale for tremor (CRST) and the quality of life in essential tremor questionnaire (QUEST). Results Right-handed tremor improved immediately after the left Vim thalamotomy in all patients. The tremor became re-exacerbated in 2 patients by 6 months after treatment; however, an approximately 60% decrease in the average CRST score of the right hand persisted until 2 years. On the other hand, the average CRST score of the left hand and the average QUEST score showed no improvement. Headache was the most common adverse event during the sonication (8 patients), followed by a floating sensation (4 patients). On the other hand, sensory disturbances (4 patients) and gait instability (4 patients) were observed after the treatment, but most of them were mild and transient. There were no delayed adverse events. Conclusion MRgFUS unilateral Vim thalamotomy could be adopted as one of the therapeutic options for intractable ET. Further improvement of tremor in the targeted hand or contralateral Vim thalamotomy may be necessary to improve the quality of life.

MRI and tractography techniques to localize the ventral intermediate nucleus and dentatorubrothalamic tract for deep brain stimulation and MR-guided focused ultrasound: a narrative review and update.

The thalamic ventral intermediate nucleus (VIM) can be targeted for treatment of tremor by several procedures, including deep brain stimulation (DBS) and, more recently, MR-guided focused ultrasound (MRgFUS). To date, such targeting has relied predominantly on coordinate-based or atlas-based techniques rather than directly targeting the VIM based on imaging features. While general regional differences of features within the thalamus and some related white matter tracts can be distinguished with conventional imaging techniques, internal nuclei such as the VIM are not discretely visualized. Advanced imaging methods such as quantitative susceptibility mapping (QSM) and fast gray matter acquisition T1 inversion recovery (FGATIR) MRI and high-field MRI pulse sequences that improve the ability to image the VIM region are emerging but have not yet been shown to have reliability and accuracy to serve as the primary method of VIM targeting. Currently, the most promising imaging approach to directly identify the VIM region for clinical purposes is MR diffusion tractography.In this review and update, the capabilities and limitations of conventional and emerging advanced methods for evaluation of internal thalamic anatomy are briefly reviewed. The basic principles of tractography most relevant to VIM targeting are provided for familiarization. Next, the key literature to date addressing applications of DTI and tractography for DBS and MRgFUS is summarized, emphasizing use of direct targeting. This literature includes 1-tract (dentatorubrothalamic tract [DRT]), 2-tract (pyramidal and somatosensory), and 3-tract (DRT, pyramidal, and somatosensory) approaches to VIM region localization through tractography.The authors introduce a 3-tract technique used at their institution, illustrating the oblique curved course of the DRT within the inferior thalamus as well as the orientation and relationship of the white matter tracts in the axial plane. The utility of this 3-tract tractography approach to facilitate VIM localization is illustrated with case examples of variable VIM location, targeting superior to the anterior commissure-posterior commissure plane, and treatment in the setting of pathologic derangement of thalamic anatomy. Finally, concepts demonstrated with these case examples and from the prior literature are synthesized to highlight several potential advantages of tractography for VIM region targeting.

Evoked Potentials During Peripheral Stimulation Confirm Electrode Location in Thalamic Subnuclei in Children With Secondary Dystonia.

Deep brain stimulation is an elective surgical intervention that improves the function and quality of life in children with dystonia and other movement disorders. Both basal ganglia and thalamic nuclei have been found to be relevant targets for treatment of dystonia in children, including the ventral intermediate nucleus of the thalamus, in which stimulation can control dystonic spasms. Electrophysiological confirmation of correct electrode location within the ventralis intermediate nucleus is thus important for the success of the surgical outcome. The present work shows the evoked potentials response during contralateral median-nerve stimulation at the wrist at low frequency (9 Hz) provides physiological evidence of the electrode's localization within the thalamus. We show the correlation between evoked potentials and magnetic resonance imaging (MRI) and computed tomography (CT) in 14 children undergoing implantation of deep brain stimulation electrodes for secondary dystonia. High fidelity and reproducibility of our results provides a new approach to ensure the electrode localization in the thalamic subnuclei.

Effect of thalamic deep brain stimulation on swallowing in patients with essential tremor.

ObjectiveDeep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) is a mainstay treatment for severe and drug‐refractory essential tremor (ET). Although stimulation‐induced dysarthria has been extensively described, possible impairment of swallowing has not been systematically investigated yet.MethodsTwelve patients with ET and bilateral VIM‐DBS with self‐reported dysphagia after VIM‐DBS were included. Swallowing function was assessed clinically and using by flexible endoscopic evaluation of swallowing in the stim‐ON and in the stim‐OFF condition. Presence, severity, and improvement of dysphagia were recorded.ResultsDuring stim‐ON, the presence of dysphagia could be objectified in all patients, 42% showing mild, 42% moderate, and 16 % severe dysphagia. During stim‐OFF, all patients experienced a statistically significant improvement of swallowing function.InterpretationVIM‐DBS may have an impact on swallowing physiology in ET‐patients. Further studies to elucidate the prevalence and underlying pathophysiological mechanisms are warranted.

Advanced MRI techniques for transcranial high intensity focused ultrasound targeting.

Magnetic resonance guided high intensity focused ultrasound is a novel, non-invasive, image-guided procedure that is able to ablate intracranial tissue with submillimetre precision. It is currently FDA approved for essential tremor and tremor dominant Parkinson's disease. The aim of this update is to review the limitations of current landmark-based targeting techniques of the ventral intermediate nucleus and demonstrate the role of emerging imaging techniques that are relevant for both magnetic resonance guided high intensity focused ultrasound and deep brain stimulation. A significant limitation of standard MRI sequences is that the ventral intermediate nucleus, dentatorubrothalamic tract, and other deep brain nuclei cannot be clearly identified. This paper provides original, annotated images demarcating the ventral intermediate nucleus, dentatorubrothalamic tract, and other deep brain nuclei on advanced MRI sequences such as fast grey matter acquisition T1 inversion recovery, quantitative susceptibility mapping, susceptibility weighted imaging, and diffusion tensor imaging tractography. Additionally, the paper reviews clinical efficacy of targeting with these novel MRI techniques when compared to current established landmark-based targeting techniques. The paper has widespread applicability to both deep brain stimulation and magnetic resonance guided high intensity focused ultrasound.

Bipolar Directional Deep Brain Stimulation in Essential and Parkinsonian Tremor

To compare directional monopolar, bipolar, and directional bipolar thalamic deep brain stimulation (DBS) in tremor patients. Fourteen tremor patients (7 Essential Tremor and 7 Parkinson's Disease) implanted with directional DBS electrodes in the ventral intermediate nucleus (VIM) were enrolled. Side-effect thresholds of monopolar directional stimulation (DIRECT) were compared to circular DBS as well as, in a randomized design, to those of two different bipolar stimulation settings (BIPOLAR = circular anode; BI-DIRECT = directional anode). Tremor suppression (Tremor Rating Scale, TRS) right below the side-effect threshold was also assessed. Directional DBS in the individually best direction showed higher side-effect thresholds than circular DBS (p = 0.0063). The thresholds were raised further using either one of the bipolar stimulation paradigms (BIPOLAR p = 0.0029, BI-DIRECT p = 0.0022). The side-effect thresholds did not differ between both bipolar settings, but side-effects were less frequent with BI-DIRECT. No difference in TRS scores with stimulation just below the side-effect threshold was found between all stimulation conditions. Side-effect thresholds of monopolar directional and bipolar stimulation with both circular and directional anodes were higher compared to traditional monopolar circular stimulation in the VIM. Bipolar DBS with directional anodes evoked side-effect less frequently than bipolar and monopolar directional stimulation. All stimulation settings had comparable effects on tremor suppression just below their side-effect thresholds. Thus, directional and different bipolar settings should be explored in patients with bothersome side-effects of thalamic stimulation when monopolar stimulation settings are not satisfying. Further studies are needed to explore the efficiency of the different bipolar stimulation paradigms.

Striatal and Thalamic Auditory Response During Deep Brain Stimulation for Essential Tremor: Implications for Psychosis

The P50, a positive auditory-evoked potential occurring 50 msec after an auditory click, has been characterized extensively with electroencephalography (EEG) to detect aberrant auditory electrophysiology in disorders like schizophrenia (SZ) where 61-74% have an auditory gating deficit. The P50 response occurs in primary auditory cortex and several thalamocortical regions. In rodents, the gated P50 response has been identified in the reticular thalamic nucleus (RT)-a deep brain structure traversed during deep brain stimulation (DBS) targeting of the ventral intermediate nucleus (VIM) of the thalamus to treat essential tremor (ET) allowing for interspecies comparison. The goal was to utilize the unique opportunity provided by DBS surgery for ET to map the P50 response in multiple deep brain structures in order to determine the utility of intraoperative P50 detection for facilitating DBS targeting of auditory responsive subterritories. We developed a method to assess P50 response intraoperatively with local field potentials (LFP) using microelectrode recording during routine clinical electrophysiologic mapping for awake DBS surgery in seven ET patients. Recording sites were mapped into a common stereotactic space. Forty significant P50 responses of 155 recordings mapped to the ventral thalamus, RT and CN head/body interface at similar rates of 22.7-26.7%. P50 response exhibited anatomic specificity based on distinct positions of centroids of positive and negative responses within brain regions and the fact that P50 response was not identified in the recordings from either the internal capsule or the dorsal thalamus. Detection of P50 response intraoperatively may guide DBS targeting RT and subterritories within CN head/body interface-DBS targets with the potential to treat psychosis and shown to modulate schizophrenia-like aberrancies in mouse models.

Early Experience With New Generation Deep Brain Stimulation Leads in Parkinson’s Disease and Essential Tremor Patients

Newer generation deep brain stimulation (DBS) systems have recently become available in the United States. Data on real-life experience are limited. We present our initial experience incorporating newer generation DBS with Parkinson's disease (PD) and essential tremor (ET) patients. Newer systems allow for smart energy delivery and more intuitive programming and hardware modifications including constant current and directional segmented contacts. We compared six-month outcomes between 42 newer generation and legacy leads implanted in 28 patients. Two cohorts each included 7 PD patients with bilateral subthalamic nucleus (STN) stimulation and 7 ET patients with unilateral ventral intermediate nucleus (VIM) stimulation of the thalamus. All directional leads included 6172 Infinity 8-Channel Directional leads and Infinity internal pulse generators (Abbott Neuromodulation, Plano, TX, USA) and nondirectional leads included lead 3389 with Activa SC for VIM and PC for STN (Medtronic, Minneapolis, MN, USA). Six-month outcomes for medication reduction and motor score improvements between new and legacy DBS systems in PD and ET patients were similar. Directionality was employed in 1/3 of patients. Therapeutic window (difference between amplitude when initial symptom relief was obtained and when intolerable side effects appeared with the contact being used) was significantly greater in new DBS systems in both PD (p = 0.005) and ET (p = 0.035) patients. The windows for new and legacy systems were 3.60 V ± 0.42 and 2.00 V ± 0.32 for STN and 3.06 V ± 0.44 and 1.85 V ± 0.28 for VIM, respectively. The therapeutic window of newer systems, whether or not directionality was used, was significantly greater than that of the legacy system, which suggests increased benefit and programming options. Improvements in hardware and programming interfaces in the newer systems may also contribute to wider therapeutic windows. We expect that as we alter workflow associated with newer technology, more patients will use directionality, and amplitudes will become lower.

Long-term efficacy and cognitive effects of voltage-based deep brain stimulation for drug-resistant essential tremor

ObjectivesTo analyze the long-term efficacy and cognitive effects of voltage-based deep brain stimulation (DBS) for drug-resistant essential tremor (ET). Patients and MethodsPatients 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. ResultsEleven 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. ConclusionFor 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.