Bilateral Thalamic Deep Brain Stimulation Research Articles

Responsive deep brain stimulation for the treatment of Tourette syndrome.

To report the results of 'responsive' deep brain stimulation (DBS) for Tourette syndrome (TS) in a National Institutes of Health funded experimental cohort. The use of 'brain derived physiology' as a method to trigger DBS devices to deliver trains of electrical stimulation is a proposed approach to address the paroxysmal motor and vocal tic symptoms which appear as part of TS. Ten subjects underwent bilateral staged DBS surgery and each was implanted with bilateral centromedian thalamic (CM) region DBS leads and bilateral M1 region cortical strips. A series of identical experiments and data collections were conducted on three groups of consecutively recruited subjects. Group 1 (n = 2) underwent acute responsive DBS using deep and superficial leads. Group 2 (n = 4) underwent chronic responsive DBS using deep and superficial leads. Group 3 (n = 4) underwent responsive DBS using only the deep leads. The primary outcome measure for each of the 8 subjects with chronic responsive DBS was calculated as the pre-operative baseline Yale Global Tic Severity Scale (YGTSS) motor subscore compared to the 6month embedded responsive DBS setting. A responder for the study was defined as any subject manifesting a ≥ 30 points improvement on the YGTSS motor subscale. The videotaped Modified Rush Tic Rating Scale (MRVTRS) was a secondary outcome. Outcomes were collected at 6months across three different device states: no stimulation, conventional open-loop stimulation, and embedded responsive stimulation. The experience programming each of the groups and the methods applied for programming were captured. There were 10 medication refractory TS subjects enrolled in the study (5 male and 5 female) and 4/8 (50%) in the chronic responsive eligible cohort met the primary outcome manifesting a reduction of the YGTSS motor scale of ≥ 30% when on responsive DBS settings. Proof of concept for the use of responsive stimulation was observed in all three groups (acute responsive, cortically triggered and deep DBS leads only). The responsive approach was safe and well tolerated. TS power spectral changes associated with tics occurred consistently in the low frequency 2-10Hz delta-theta-low alpha oscillation range. The study highlighted the variety of programming strategies which were employed to achieve responsive DBS and those used to overcome stimulation induced artifacts. Proof of concept was also established for a single DBS lead triggering bi-hemispheric delivery of therapeutic stimulation. Responsive DBS was applied to treat TS related motor and vocal tics through the application of three different experimental paradigms. The approach was safe and effective in a subset of individuals. The use of different devices in this study was not aimed at making between device comparisons, but rather, the study was adapted to the current state of the art in technology. Overall, four of the chronic responsive eligible subjects met the primary outcome variable for clinical effectiveness. Cortical physiology was used to trigger responsive DBS when therapy was limited by stimulation induced artifacts.

Disbalanced recruitment of crossed and uncrossed cerebello-thalamic pathways during deep brain stimulation is predictive of delayed therapy escape in essential tremor

BackgroundThalamic deep brain stimulation (DBS) is an efficacious treatment for drug-resistant essential tremor (ET) and the dentato-rubro-thalamic tract (DRT) constitutes an important target structure. However, up to 40% of patients habituate and lose treatment efficacy over time, frequently accompanied by a stimulation-induced cerebellar syndrome. The phenomenon termed delayed therapy escape (DTE) is insufficiently understood. Our previous work showed that DTE clinically is pronounced on the non-dominant side and suggested that differential involvement of crossed versus uncrossed DRT (DRTx/DRTu) might play a role in DTE development. MethodsWe retrospectively enrolled right-handed patients under bilateral thalamic DBS >12 months for ET from a cross-sectional study. They were characterized with the Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) and Scale for the Assessment and Rating of Ataxia (SARA) scores at different timepoints. Normative fiber tractographic evaluations of crossed and uncrossed cerebellothalamic pathways and volume of activated tissue (VAT) studies together with [18F]Fluorodeoxyglucose positron emission tomography were applied. ResultsA total of 29 patients met the inclusion criteria. Favoring DRTu over DRTx in the non-dominant VAT was associated with DTE (R2 = 0.4463, p < 0.01) and ataxia (R2 = 0.2319, p < 0.01). Moreover, increasing VAT size on the right (non-dominant) side was associated at trend level with more asymmetric glucose metabolism shifting towards the right (dominant) dentate nucleus. ConclusionOur results suggest that a disbalanced recruitment of DRTu in the non-dominant VAT induces detrimental stimulation effects on the dominant cerebellar outflow (together with contralateral stimulation) leading to DTE and thus hampering the overall treatment efficacy.

Thalamic Deep Brain Stimulation May Improve Restless Legs Syndrome in Patients With Essential Tremor

ObjectivesTo determine change in restless legs syndrome (RLS) symptoms in essential tremor (ET) patients undergoing bilateral thalamic ventral intermedius (VIM) deep brain stimulation (DBS) surgery. Materials and MethodsWe retrospectively reviewed our database of ET patients with RLS who had undergone VIM DBS for tremor from 2012 to 2020. We reviewed the patients with available International Restless Leg Syndrome Study Group RLS scale scores before and after DBS. Percentage of responders, defined as proportion of patients experiencing three or more point improvement of RLS scores post-DBS, was calculated. We performed two-tailed t-test of pre-DBS and post-DBS RLS scores. ResultsWe identified 13 patients with ET and RLS who had undergone bilateral VIM DBS, of whom nine (69%) were responders post-DBS. Five of 13 patients (38%) had complete resolution of RLS post-DBS. For all patients, mean pre-DBS RLS score was 15.8 ± 7.9 which improved by 46% post-DBS to a mean of 8.5 ± 8.8 (p = 0.007). Four patients rated their RLS scale one night with the stimulator OFF and another night with the stimulator ON. The mean RLS score with stimulator ON was 15.5 ± 7.6 which improved by 53% to a mean of 6.25 ± 7.8 (p = 0.008), with two having complete resolution of RLS with stimulator ON. Of the nine responders, six preferred to keep their stimulator ON at night due to relief of RLS and better subjective quality of sleep. ConclusionsWe report for the first time improvement of RLS in patients with ET after bilateral thalamic DBS. Although many ET patients with nonrechargeable DBS systems switch off their stimulator at night to conserve battery life, those with RLS may potentially benefit from keeping their stimulator ON at night to relieve their RLS.

P 53 Connectivity analysis to predict DBS-induced ataxia in essential tremor

Introduction: Deep Brain Stimulation (DBS) of the (sub)thalamic nucleus has been shown to be an effective treatment in medication-refractory Essential Tremor (ET). However, studies have reported a DBS-induced ataxia in some patients which can onset years after the start of DBS-therapy. In the ongoing debate on the cause a functional disruption of the cerebello-thalamo-cortical network is considered. In a previous study regions linked to stimulation induced side effects in the SCN, primary motor cortex, putamen, red nucleus and the posterior parietal cortex were identified. In this study we aim to test if the proposed connectivity to these nodes is associated with side-effects and could enable patient individual risk-predictions. Materials & Methods: In this study 50 patients (27 males; age 66±10 years; disease duration: 33±19 years) with Essential Tremor and bilateral thalamic DBS were clinically examined based on videos before surgery and at a follow up at least 3 years later using the Fahn-Tolosa-Martin scale (FTM) and the first three items of the scale for the assessment and rating of ataxia (SARA). Structural connectivity was estimated using a normative connectome and seeding the individual volumes of tissue activated (VTAs). Connectivity to the cortical regions previously linked to side effects was compared to the long-term tremor improvement as well to symptoms of ataxia. Based on an ordinal logistic regression analysis the best prediction model using patients‘ connectivity to these regions was identified. Using data of 40 randomly selected patients of the cohort to train the algorithm it was then tested against the remaining 10 patients. Results: On average tremor improved by 11±10 points on the FTM-scale and the SARA-score worsened by -2±2 points. Mild ataxia occurred in 21 patients and 5 patients showed severe ataxia. The normative structural connectivity to the entirety of the nodes correlated significantly to a worsening of ataxia (p < 0.01) but not to overall tremor control (p = 0.34). The best network-model prediction was based on connectivity to nodes in the primary motor cortex and the posterior parietal cortex and was able to correctly predict and categorize side effects in 7 out of 10 patients of the test cohort. Conclusion: This study supports the association of the predescribed cortical nodes to a network tied to stimulation induced ataxia side-effects in ET-patients. The results indicate that models based on the connectivity to this network could aid in the risk assessment of patients and improve individual outcome in the future.

Thalamic Deep Brain Stimulation Ameliorates Mixed and Abductor Spasmodic Dysphonia: Case Reports and Proof of Concept

Abstract BACKGROUND AND IMPORTANCE Spasmodic dysphonia (SD) is a dystonia of the vocal folds causing difficulty with speech. A recent randomized controlled trial showed that thalamic deep brain stimulation (DBS) was safe and could improve this condition in the most common subtype—adductor SD. We investigated if thalamic DBS could also improve the other subtypes of abductor SD and mixed SD. These prospective blinded trials of 1 were designed to assess the safety of thalamic DBS in mixed and abductor SD and to quantify the magnitude of any benefit from unilateral or bilateral thalamic stimulation. CLINICAL PRESENTATION One patient with mixed SD and one patient with abductor SD received bilateral thalamic DBS. After optimizing their DBS settings for vocal improvement, they were blinded and prospectively randomized to receive 1 mo of left, right, both, or neither hemisphere stimulation. Outcome was assessed by a speech language pathologist, blinded to the settings, rating voice recordings with the Unified Spasmodic Dysphonia Rating Scale, and by patient self-reported quality-of-life questionnaires. Additional outcomes included scores of mood and cognition. There were no complications. Both patients reported a subjective improvement of their voice and quality of life with blinded left thalamic DBS. The quality of their voice was also objectively rated as improved with blinded left thalamic DBS. CONCLUSION This small proof-of-concept study suggests that left thalamic DBS can improve the quality of voice and quality of life of patients with mixed SD and abductor SD.

Tremor and Quality of Life in Patients With Advanced Essential Tremor Before and After Replacing Their Standard Deep Brain Stimulation With a Directional System

ObjectivesPatients with essential tremor treated with thalamic deep brain stimulation may experience increased tremor with the progression of their disease. Initially, this can be counteracted with increased stimulation. Eventually, this may cause unwanted side-effects as the circumferential stimulation from a standard ring contact spreads into adjacent regions. Directional leads may offer a solution to this clinical problem. We aimed to compare the ability of a standard and a directional system to reduce tremor without side-effects and to improve the quality of life for patients with advanced essential tremor. Materials and MethodsSix advanced essential tremor patients with bilateral thalamic deep brain stimulation had their standard system replaced with a directional system. Tremor rating scale scores were prospectively evaluated before and after the replacement surgery. Secondary analyses of quality of life related to tremor, voice, and general health were assessed. ResultsThere was a significantly greater reduction in tremor without side-effects (p = 0.017) when using the directional system. There were improvements in tremor (p = 0.031) and voice (p = 0.037) related quality of life but not in general health for patients using optimized stimulation settings with the directional system compared to the standard system. ConclusionsIn this cohort of advanced essential tremor patients who no longer had ideal tremor reduction with a standard system, replacing their deep brain stimulation with a directional system significantly improved their tremor and quality of life. Up-front implantation of directional deep brain stimulation leads may provide better tremor control in those patients who progress at a later time point.

Selecting the Most Effective DBS Contact in Essential Tremor Patients Based on Individual Tractography.

Postoperative choice of the most effective deep brain stimulation (DBS) contact in patients with essential tremor (ET) so far relies on lengthy clinical testing. Previous studies showed that the postoperative effectiveness of DBS contacts depends on the distance to the dentatorubrothalamic tract (DRTT). Here, we investigated whether the most effective DBS contact could be determined from calculating stimulation overlap with the individual DRTT. Seven ET patients with bilateral thalamic deep brain stimulation were included retrospectively. Tremor control was assessed for each contact during test stimulation with 2mA. Individual DRTTs were identified from diffusion tensor imaging and contacts were ranked by their stimulation overlap with the respective DRTT in relation to their clinical effectiveness. A linear mixed-effects model was calculated to determine the influence of the DRTT overlap on tremor control. In all investigated DBS leads, the contact with the best clinical effect was the contact with the highest or second-highest DRTT-overlap. At the group level, the DRTT-overlap explained 26.7% of the variance in the clinical outcomes (p < 0.001). Our data suggest that the overlap with the DRTT based on individual tractography may serve as a marker to determine the most effective DBS contact in ET patients and reduce burdensome clinical testing in the future.

Network Fingerprint of Stimulation-Induced Speech Impairment in Essential Tremor.

This study was undertaken to gain insights into structural networks associated with stimulation-induced dysarthria (SID) and to predict stimulation-induced worsening of intelligibility in essential tremor patients with bilateral thalamic deep brain stimulation (DBS). Monopolar reviews were conducted in 14 essential tremor patients. Testing included determination of SID thresholds, intelligibility ratings, and a fast syllable repetition task. Volumes of tissue activated (VTAs) were calculated to identify discriminative fibers for stimulation-induced worsening of intelligibility in a structural connectome. The resulting fiber-based atlas structure was then validated in a leave-one-out design. Fibers determined as discriminative for stimulation-induced worsening of intelligibility were mainly connected to the ipsilateral precentral gyrus as well as to both cerebellar hemispheres and the ipsilateral brain stem. In the thalamic area, they ran laterally to the thalamus and posteromedially to the subthalamic nucleus, in close proximity, mainly anterolaterally, to fibers beneficial for tremor control as published by Al-Fatly et al in 2019. The overlap of the respective clinical stimulation setting's VTAs with these fibers explained 62.4% (p < 0.001) of the variance of stimulation-induced change in intelligibility in a leave-one-out analysis. This study demonstrates that SID in essential tremor patients is associated with both motor cortex and cerebellar connectivity. Furthermore, the identified fiber-based atlas structure might contribute to future postoperative programming strategies to achieve optimal tremor control without speech impairment in essential tremor patients with thalamic DBS. ANN NEUROL 2021;89:315-326.

Cortex leads the thalamic centromedian nucleus in generalized epileptic discharges in Lennox-Gastaut syndrome.

We aimed to assess the roles of the cortex and thalamus (centromedian nucleus [CM]) during epileptic activity in Lennox-Gastaut syndrome (LGS) patients undergoing deep brain stimulation (DBS) surgery as part of the ESTEL (Electrical Stimulation of the Thalamus for Epilepsy of Lennox-Gastaut Phenotype) trial. Twelve LGS patients (mean age=26.8years) underwent bilateral CM-DBS implantation. Intraoperatively, simultaneous electroencephalogram (EEG) was recorded (range=10-34 minutes) from scalp electrodes and bilateral thalamic DBS electrodes. Temporal onsets of epileptic discharges (generalized paroxysmal fast activity [GPFA] and slow spike-and-wave [SSW]) were manually marked on recordings from scalp (ie, "cortex") and thalamus (ie, CM-DBS electrodes). Phase transfer entropy (PTE) analysis quantified the degree of information transfer from cortex to thalamus within different frequency bands around GPFA events. GPFA was captured in eight of 12 patients (total event number across patients=168, cumulative duration=358seconds). Eighty-six percent of GPFA events were seen in both scalp and thalamic recordings. In most events (83%), onset occurred first at scalp, with thalamic onset lagging by a median of 98milliseconds (interquartile range=78.5milliseconds). Results for SSW were more variable and seen in 11 of 12 patients; 25.4% of discharges were noted in both scalp and thalamus. Of these, 74.5% occurred first at scalp, with a median lag of 75milliseconds (interquartile range=228milliseconds). One to 0.5seconds and 0.5-0seconds before GPFA onset, PTE analysis showed significant energy transfer from scalp to thalamus in the delta (1-3Hz) frequency band. For alpha (8-12Hz) and beta (13-30Hz) frequencies, PTE was greatest 1-0.5seconds before GPFA onset. Epileptic activity is detectable in CM of thalamus, confirming that this nucleus participates in the epileptic network of LGS. Temporal onset of GPFA mostly occurs earlier at the scalp than in the thalamus. This supports our prior EEG-functional magnetic resonance imaging results and provides further evidence for a cortically driven process underlying GPFA in LGS.

Issue highlights

Fleisher et al. (p. 277) conducted a pilot study on disease severity and quality of life (QoL) in homebound individuals with advanced Parkinson disease. The authors report high retention and satisfaction with quarterly interdisciplinary home visits and stabilization of QoL in an often-overlooked population. Hewitt et al. (p. 324) evaluated a single case series of 5 patients with medication-refractory orthostatic tremor who were treated with bilateral VIM thalamic deep brain stimulation. Patients experienced a modest increase of up to several minutes in standing time, which translated to meaningful improvement in standing activities of daily living.

Deep brain stimulation for orthostatic tremor: A single-center case series.

Orthostatic tremor (OT) is a high-frequency weight-bearing tremor of the legs and trunk associated with progressive disability and is often refractory to medications. Case reports suggest that thalamic deep brain stimulation (DBS) is effective. We report 5 female patients with medication-refractory OT who underwent bilateral thalamic DBS at the Mayo Clinic and assess factors associated with a successful DBS outcome. Demographic, clinical, electrophysiology, and DBS data were abstracted. Outcomes were change in tremor-onset latency, standing time, standing ADLs, and patient and clinician global impression of change (PGIC; CGIC). All 5 patients had improved standing time (72 vs 408 seconds, p ≤ 0.001) and improved standing ADLs after surgery, without change in tremor-onset latency (16 vs 75 seconds, p = 0.14). Maximal benefit was reached up to 3 years after surgery and sustained for up to 6 years. CGIC was "much improved" in all; PGIC was "much improved" in 4 and "minimally improved" in 1. There were no major complications. Postoperative electrophysiology (n = 1) showed lower tremor amplitude and slower tremor ramp-up on vs off stimulation. Bilateral thalamic DBS improved OT symptoms with benefit lasting up to 6 years. A modest increase in standing time of several minutes was associated with meaningful improvement in standing ADLs. Microlesional effect and bilateral stimulation are likely favorable features, while baseline standing time of several minutes may be unfavorable. These findings may inform clinician and patient counseling and require confirmation in larger studies.

Pallidal and thalamic neural oscillatory patterns in tourette's syndrome.

Aberrant oscillatory activity has been hypothesized to play a role in the pathophysiology of Tourette's syndrome (TS). Deep brain stimulation (DBS) has recently been established as an effective treatment for severe TS. Modulation of symptom-specific oscillations may underlie the mechanism of action of DBS and could be used for adaptive neuromodulation to improve therapeutic efficacy. The objective of this study was to demonstrate a pathophysiological association of pallidal and thalamic local field potentials (LFPs) with TS. Nine medication-refractory TS patients were included in the study. Intracerebral LFPs were recorded simultaneously from bilateral pallidal and thalamic DBS electrodes. Spectral and temporal dynamics of pallidal and thalamic oscillations were characterized and correlated with preoperative Yale Global Tic Severity Scale (YGTSS) scores. Peaks of activity in the theta (3-12Hz) and beta (13-35Hz) were present in pallidal and thalamic recordings from all patients (3 women/6 men; mean age, 29.8 years) and coupled through coherence across targets. Presence of prolonged theta bursts in both targets was associated with preoperative motor tic severity. Total preoperative YGTSS scores (mean, 38.1) were correlated with pallidal and thalamic LFP activity using multivariable linear regression (R² = 0.96; p = 0.02). Our findings suggest that pallidothalamic oscillations may be implicated in the pathophysiology of TS. Furthermore, our results highlight the utility of multisite and -spectral oscillatory features in severely affected patients for future identification and clinical use of oscillatory physiomarkers for adaptive stimulation in TS. Ann Neurol 2018;84:505-514.

Orthostatic Tremor is Responsive to Bilateral Thalamic Deep Brain Stimulation: Report of Two Cases Performed Asleep

<strong>Background:</strong> Orthostatic tremor (OT) is a hyperkinetic movement disorder characterized by rapid tremor in the lower extremities or trunk upon standing. <strong>Case Report:</strong> We report two patients presenting with OT, whose symptoms improved markedly following asleep bilateral thalamic deep brain stimulation (DBS) surgery. <strong>Discussion:</strong> Medically refractory OT can respond favorably to asleep bilateral DBS surgery similar to awake surgery, and may have the advantages of less psychological trauma to the patient, shorter procedure times, and less exposure to anesthesia.

The Effect of Deep Brain Stimulation (DBS) for Voice Tremor in a Case of Essential Tremor

Patients with voice tremor present with shaking voice which has a frequency of 4-5 Hz in their vocal tract. In most of cases, voice tremor is refractory to conservative treatment such as medication or voice therapy and the symptoms may affect a patient’s quality of life. We experienced a case of voice tremor accompanied by essential tremor of the upper extremities who was treated with bilateral thalamic deep brain stimulation (DBS). The results of an acoustic analysis and laryngeal endoscopic findings showed a partial improvement following unilateral DBS and complete improvement following bilateral DBS. FTRI, Fatr, ATRI, Jitter, Shimmer, vF0, vAm, NHR, sPPQ and sAPQ seemed to be useful parameters of voice tremor. The results suggest that the indication of DBS should be discussed for patients severely affected by voice tremor after considering the patient’s age, accompanying symptoms, backgrounds, occupation and needs.

Management of Elevated Therapeutic Impedances on Deep Brain Stimulation Leads.

Clinical VignetteA 64-year-old male with a history of essential tremor with bilateral thalamic ventralis intermedius deep brain stimulation implants had elevated therapeutic impedance values despite normal lead integrity impedances and good response to stimulation.Clinical DilemmaDo elevated therapeutic impedance values indicate a sign of hardware malfunction? What are the guidelines to approach deep brain stimulation hardware malfunction?Clinical SolutionLead integrity impedance values are a better evaluation of hardware integrity. The discrepancy between therapeutic and lead-integrity impedance values can arise when using low voltage settings.Gaps in KnowledgeThere are no established guidelines for the management of possible hardware malfunction in deep brain stimulation. The recommended approach is to distinguish between open and short circuit problems followed by an “inching” evaluation, assessing the structures from the implantable and programmable generator to the intracranial leads. Constant-current devices will deliver a more stable stimulation but the effect of their adoption is still not clear.Expert CommentaryThis case emphasizes the need for clinicians to understand fundamental differences in lead integrity and therapeutic impedance while utilizing a methodical approach in treating hardware malfunction. It highlights future avenues of investigation regarding the utility of constant current DBS technology.

Management of Elevated Therapeutic Impedances on Deep Brain Stimulation Leads

<strong>Clinical Vignette:</strong> A 64-year-old male with a history of essential tremor with bilateral thalamic ventralis intermedius deep brain stimulation implants had elevated therapeutic impedance values despite normal lead integrity impedances and good response to stimulation. <strong>Clinical Dilemma:</strong> Do elevated therapeutic impedance values indicate a sign of hardware malfunction? What are the guidelines to approach deep brain stimulation hardware malfunction? <strong>Clinical Solution:</strong> Lead integrity impedance values are a better evaluation of hardware integrity. The discrepancy between therapeutic and lead-integrity impedance values can arise when using low voltage settings. <strong>Gaps in Knowledge:</strong> There are no established guidelines for the management of possible hardware malfunction in deep brain stimulation. The recommended approach is to distinguish between open and short circuit problems followed by an ‘‘inching’’ evaluation, assessing the structures from the implantable and programmable generator to the intracranial leads. Constant-current devices will deliver a more stable stimulation but the effect of their adoption is still not clear. <strong>Expert Commentary:</strong> This case emphasizes the need for clinicians to understand fundamental differences in lead integrity and therapeutic impedance while utilizing a methodical approach in treating hardware malfunction. It highlights future avenues of investigation regarding the utility of constant current DBS technology.

Bilateral thalamic deep brain stimulation for essential tremor in elderly patients.

The purpose of this study was to assess the influence of age on thalamic deep brain stimulation (DBS) in essential tremor (ET). Tremor, cognition, mood and adverse events in patients with thalamic DBS for ET were evaluated in 26 consecutive patients with established standardized methods for tremor and cognition. Twelve patients <70 and 14 patients ≥70years were included and followed for 2years. Clinical outcomes did not differ significantly. DBS seems to be safe and effective for ET independent of age.

The Effect of Uni- and Bilateral Thalamic Deep Brain Stimulation on Speech in Patients With Essential Tremor: Acoustics and Intelligibility

Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) is performed to suppress medically-resistant essential tremor (ET). However, stimulation induced dysarthria (SID) is a common side effect, limiting the extent to which tremor can be suppressed. To date, the exact pathogenesis of SID in VIM-DBS treated ET patients is unknown. We investigate the effect of inactivated, uni- and bilateral VIM-DBS on speech production in patients with ET. We employ acoustic measures, tempo, and intelligibility ratings and patient's self-estimated speech to quantify SID, with a focus on comparing bilateral to unilateral stimulation effects and the effect of electrode position on speech. Sixteen German ET patients participated in this study. Each patient was acoustically recorded with DBS-off, unilateral-right-hemispheric-DBS-on, unilateral-left-hemispheric-DBS-on, and bilateral-DBS-on during an oral diadochokinesis task and a read German standard text. To capture the extent of speech impairment, we measured syllable duration and intensity ratio during the DDK task. Naïve listeners rated speech tempo and speech intelligibility of the read text on a 5-point-scale. Patients had to rate their "ability to speak". We found an effect of bilateral compared to unilateral and inactivated stimulation on syllable durations and intensity ratio, as well as on external intelligibility ratings and patients' VAS scores. Additionally, VAS scores are associated with more laterally located active contacts. For speech ratings, we found an effect of syllable duration such that tempo and intelligibility was rated worse for speakers exhibiting greater syllable durations. Our data confirms that SID is more pronounced under bilateral compared to unilateral stimulation. Laterally located electrodes are associated with more severe SID according to patient's self-ratings. We can confirm the relation between diadochokinetic rate and SID in that listener's tempo and intelligibility ratings can be predicted by measured syllable durations from DDK tasks.

Precise stimulation location optimizes speech outcomes in essential tremor

BackgroundDeep brain stimulation for essential arm tremor is often complicated by dysarthria and persistent voice tremor. ObjectiveTo determine the relationship of stimulation location to speech outcomes following bilateral thalamic deep brain stimulation (DBS) for essential tremor (ET). MethodsEighteen patients undergoing bilateral DBS for ET were prospectively studied. Speech pathologists grouped patients by final speech outcome (normal speech, voice tremor, or dysarthria). Locations of the active leads were calculated by normalizing the segmented thalamic volumes to those in the Morel atlas. Stimulation volumes within thalamic nuclei, error distances from target, and measures of accuracy were calculated and differences in measures between outcome groups tested. ResultsAt optimal stimulation, 8 patients had normal speech, 6 had voice tremor, and 4 had mild dysarthria. Stimulation volumes were statistically concentrated within the ventral lateral posterior nucleus (VLp). The percentage of stimulation volume outside the VLp was higher in patients with dysarthria (60% vs. 24%, p = 0.02) or voice tremor (55% vs. 24%, p = 0.03) compared to patients with normal speech outcomes. The error distance from the center of VLp was greater for patients with dysarthria than those with normal speech (12.6 vs. 7.6 mm, p = 0.02). Electrodes with lower efficiency for VLp stimulation were more frequent with poor speech outcomes and in patients with persistent voice tremor. ConclusionsFollowing bilateral DBS for ET, 22% of patients develop a non-disabling dysarthria. Optimal speech outcomes were achieved in 44% of patients and correlated with precise stimulation location within and not outside of the VLp.

EP 14. Clinical experiences with long term thalamic deep brain stimulation in severe Tourette Syndrome

Introduction Thalamic deep brain stimulation is effective in reducing tics in patients with severe Tourette syndrome at the short-term. Here, we report on the long-term outcome. Methods Seven patients with refractory Tourette syndrome were referred to the Maastricht University Medical Centre and underwent bilateral thalamic deep brain stimulation between 2001 and 2008. The target was the centromedian nucleus-substantia periventricularis-nucleus ventro-oralis internus cross point of the thalamus. During the visits to the outpatient clinic, effects on tics, side-effects and stimulations parameters were evaluated. The follow-up duration varied between 12 to 78 months. Results Patient 1 showed an improvement on tics of 81.6% after 60 months, but due to higher voltage stimulation after some years needed to suppress the tics, side-effects became more severe and the target was changed to the anterior part of the internal pallidum. Patient 2 showed a tic improvement of 50% after 36 months, but due to increasing side-effects, he switched the stimulator permanently off. In patient 3 the stimulator is still active and showed satisfying results with an improvement on tics of 88.9% after 78 months. Patient 4 experienced a tic improvement of 34% after 16 months. However, side-effects became more severe, and when the whole system had to be removed due to a persisting hardware infection after six years, the target was changed to the anterior part of the internal pallidum. Patient 5 showed a minor tic improvement of 27.5% after 12 months. He was unsatisfied and went to abroad for stimulation of the external globus pallidus. Patient 6 developed cerebral atrophy due to a neurodegenerative disease and experienced several non-stimulation related side-effects. His tic improvement was 34% on the YGTSS after 26 months and he decided to turn the stimulator off. The positive effect on tics in patient 7 decreased over time until an improvement of only 9% at 60 months of follow-up. The target was changed to the anterior part of the internal pallidum. Conclusion Thalamic deep brain stimulation in patients with severe Tourette syndrome is effective in reducing tics, at least at the short-term. At the long-term only in one patient the stimulator is still active, in three patients the target was changed to the anterior part of the internal pallidum due to side-effects and three were unsatisfied and turned off their stimulator. There seems to be an increasing disbalance of effects versus side effects leading to either switching off the stimulator or re-surgery changing the target. These clinical cases reflect the strong heterogeneity of the disease, with serious comorbity, interfering with effects and side-effects of deep brain stimulation.