Stimulation In Dystonia Research Articles

Functional imaging of deep brain stimulation in dystonia: a review

Much remains to be learned about the mechanism of benefit of deep brain stimulation in movement disorders in general and dystonia specifically. A full accounting of the pathophysiology of dystonia additionally remains unclear. Given its ability to evaluate whole-brain network changes, functional neuroimaging is an important tool to advance understanding of the effects of deep brain stimulation, which in turn could offer insight into the pathophysiology of dystonia and suggest novel deep brain stimulation targets for the disorder. This review surveys the published literature of functional neuroimaging studies evaluating deep brain stimulation effects in dystonia, including PET, SPECT, and functional MRI studies. To date, study cohorts have been relatively small, though several general patterns emerge when studies are viewed collectively, including reduced functional activation patterns with stimulation turned on during motor tasks, particularly in frontal cortical regions. During rest with stimulation on, several studies showed areas of relatively decreased perfusion only in those participants who experienced clinical benefit from deep brain stimulation. Future research may benefit from larger cohorts with more homogeneous forms of dystonia, potentially enabled by multi-center initiatives. Additional benefits may result from more detailed longitudinal assessments and greater use of functional MRI, with study designs that take into account the technical limitations of this modality in the context of movement disorders and deep brain stimulation.

Deep brain stimulation in dystonia: The added value of neuropsychological assessments.

Deep brain stimulation (DBS) of the internal globus pallidus (GPi) is a recognized treatment for medication-refractory dystonia. Problems in executive functions and social cognition can be part of dystonia phenotypes. The impact of pallidal DBS on cognition appears limited, but not all cognitive domains have been investigated yet. In the present study, we compare cognition before and after GPi DBS. Seventeen patients with dystonia of various aetiology completed pre- and post-DBS assessment (mean age 51 years; range 20-70 years). Neuropsychological assessment covered intelligence, verbal memory, attention and processing speed, executive functioning, social cognition, language and a depression questionnaire. Pre-DBS scores were compared with a healthy control group matched for age, gender and education, or with normative data. Patients were of average intelligence but performed significantly poorer than healthy peers on tests for planning and for information processing speed. Otherwise, they were cognitively unimpaired, including social cognition. DBS did not change the baseline neuropsychological scores. We confirmed previous reports of executive dysfunctions in adult dystonia patients with no significant influence of DBS on cognitive functioning in these patients. Pre-DBS neuropsychological assessments appear useful as they support clinicians in counselling their patients. Decisions about post-DBS neuropsychological evaluations should be made on a case-by-case basis.

Restoration of functional network state towards more physiological condition as the correlate of clinical effects of pallidal deep brain stimulation in dystonia

BackgroundDeep brain stimulation of the internal globus pallidus (GPi DBS) is an invasive therapeutic modality intended to retune abnormal central nervous system patterns and relieve the patient of dystonic or other motor symptoms. ObjectivesThe aim of the presented research was to determine the neuroanatomical signature of GPi DBS modulation and its association with the clinical outcome. MethodsThis open-label fixed-order study with cross-sectional validation against healthy controls analysed the resting-state functional MRI activity changes induced by GPi DBS in 18 dystonia patients of heterogeneous aetiology, focusing on both global (full brain) and local connectivity (local signal homogeneity). ResultsCompared to the switched-off state, the activation of GPi DBS led to the restoration of global subcortical connectivity patterns (in both putamina, diencephalon and brainstem) towards those of healthy controls, with positive direct correlation over large-scale cortico-basal ganglia-thalamo-cortical and cerebellar networks with the clinical improvement. Nonetheless, on average, GPi DBS also seemed to bring local connectivity both in the cortical and subcortical regions farther away from the state detected in healthy controls. Interestingly, its correlation with clinical outcome showed that in better DBS responders, local connectivity defied this effect and approached healthy controls. ConclusionsAll in all, the extent of restoration of both these main metrics of interest towards the levels found in healthy controls clearly correlated with the clinical improvement, indicating that the restoration of network state towards more physiological condition may be a precondition for successful GPi DBS outcome in dystonia.

Deep brain stimulation in dystonia: factors contributing to variability in outcome in short and long term follow-up.

Deep brain stimulation (DBS) is currently the most effective treatment for medically refractory dystonia with globus pallidus internus (GPi) usually the preferred target. Despite the overall success of DBS in dystonia, there remains variability in treatment outcome in both short and long-term follow-up, due to various factors. Factors contributing to variability in outcome comprise 'Dystonia Related' including dystonia classification, semiology, duration, body distribution, orthopaedic deformity, aetiology and genetic cause. The majority of these factors are identifiable from clinical assessment, brain MRI and genetic testing, and therefore merit careful preoperative consideration. 'DBS related' factors include brain target, accuracy of lead placement, stimulation parameters, time allowed for response, neurostimulation technology employed and DBS induced side-effects. In this review, factors contributing to variability in short and long-term dystonia DBS outcome are reviewed and discussed. The recognition of differential DBS benefit in monogenic dystonia, increasing experience with subthalamic nucleus (STN) DBS and in DBS for Meige syndrome, elucidation of DBS side effects and novel neurophysiological and imaging techniques to assist in predicting clinical outcome. Improved understanding of factors contributing to variability of DBS outcome in dystonia may assist in patient selection and predicting surgical outcomes.

Exploring the connections between basal ganglia and cortex revealed by transcranial magnetic stimulation, evoked potential and deep brain stimulation in dystonia.

We review the findings for motor cortical excitability, plasticity and evoked potentials in dystonia. Plasticity can be induced and assessed in cortical areas by non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and the invasive technique of deep brain stimulation (DBS), which allows access to deep brain structures. Single-pulse TMS measures have been widely studied in dystonia and consistently showed reduced silent period duration. Paired pulse TMS measures showed reduced short and long interval intracortical inhibition, interhemispheric inhibition, long-latency afferent inhibition and increased intracortical facilitation in dystonia. Repetitive transcranial magnetic stimulation (rTMS) of the premotor cortex improved handwriting with prolongation of the silent period in focal hand dystonia patients. Continuous theta-burst stimulation (cTBS) of the cerebellum or cTBS of the dorsal premotor cortex improved dystonia in some studies. Plasticity induction protocols in dystonia demonstrated excessive motor cortical plasticity with the reduction in cortico-motor topographic specificity. Bilateral DBS of the globus pallidus internus (GPi) improves dystonia, associated pain and functional disability. Local field potentials recordings in dystonia patients suggested that there is increased power in the low-frequency band (4-12Hz) in the GPi. Cortical evoked potentials at peak latencies of 10 and 25ms can be recorded with GPi stimulation in dystonia. Plasticity induction protocols based on the principles of spike timing dependent plasticity that involved repeated pairing of GPi-DBS and motor cortical TMS at latencies of cortical evoked potentials induced motor cortical plasticity. These studies expanded our knowledge of the pathophysiology of dystonia and how cortical excitability and plasticity are altered with different treatments such as DBS.

Effects of non-invasive brain stimulation in dystonia: a systematic review and meta-analysis.

Deep brain stimulation is a highly effective treatment of dystonia but is invasive and associated with risks, such as intraoperative bleeding and infections. Previous research has used non-invasive brain stimulation (NIBS) in an attempt to alleviate symptoms of dystonia. The results of these studies, however, have been variable, leaving efficacy unclear. This study aimed to evaluate the effects of NIBS on symptoms of dystonia and determine whether methodological characteristics are associated with variability in effect size. Web of Science, Embase, and MEDLINE Complete databases were searched for articles using any type of NIBS as an intervention in dystonia patients, with changes in dystonia symptoms the primary outcome of interest. Meta-analysis of 27 studies demonstrated a small effect size for NIBS in reducing symptoms of dystonia (random-effects Hedges' g = 0.21, p = .002). Differences in the type of NIBS, type of dystonia, and brain region stimulated had a significant effect on dystonia symptoms. Meta-regression revealed that 10 sessions of active stimulation and the application of concurrent motor training programs resulted in significantly larger mean effect sizes. NIBS has yielded small improvements to dystonic symptoms, but effect sizes depended on methodological characteristics, with more sessions of stimulation producing a larger response. Future research should further investigate the application of NIBS parallel to motor training, in addition to providing a greater quantity of sessions, to help define optimal parameters for NIBS protocols in dystonia. PROSPERO 2020, CRD42020175944.

The Effectiveness of Deep Brain Stimulation in Dystonia: A Patient-Centered Approach.

Background:To systematically evaluate the effectiveness of deep brain stimulation of the globus pallidus internus (GPi-DBS) in dystonia on pre-operatively set functional priorities in daily living.Methods:Fifteen pediatric and adult dystonia patients (8 male; median age 32y, range 8–65) receiving GPi-DBS were recruited. All patients underwent a multidisciplinary evaluation before and 1-year post DBS implantation. The Canadian Occupational Performance Measure (COPM) first identified and then measured changes in functional priorities. The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to evaluate dystonia severity.Results:Priorities in daily functioning substantially varied between patients but showed significant improvements on performance and satisfaction after DBS. Clinically significant COPM-score improvements were present in 7/8 motor responders, but also in 4/7 motor non-responders.Discussion:The use of a patient-oriented approach to measure GPi-DBS effectiveness in dystonia provides an unique insight in patients’ priorities and demonstrates that tangible improvements can be achieved irrespective of motor response.HighlightsFunctional priorities in life of dystonia patients and their caregivers vary greatlyThe effect of DBS on functional priorities did not correlate with motor outcomeHalf of the motor ‘non-responder’ patients reported important changes in their prioritiesThe effect of DBS in dystonia should not be measured by motor outcome alone

Long-term effects of bilateral pallidal deep brain stimulation in dystonia: a follow-up between 8 and 16\xa0years

ObjectiveObservational study to evaluate the long-term motor and non-motor effects of deep brain stimulation (DBS) of the globus pallidus internus (GPi) on medically refractory dystonia.BackgroundDystonia is a chronic disease affecting mainly young patients with a regular life expectancy and lifelong need for therapy. Pallidal DBS is an established treatment for severe isolated dystonia but long-term data are sparse.MethodsWe considered 36 consecutive patients with isolated generalized (n = 14) and cervical/segmental (n = 22) dystonia operated at Charité-University Hospital between 2000 and 2007 in a retrospective analysis for long-term outcome of pallidal DBS. In 19 of these patients, we could analyze dystonic symptoms and disability rated by the Burke–Fahn–Marsden Dystonia Rating scale (BFMDRS) at baseline, short-term (ST-FU, range 3–36 months) and long-term follow-up (LT-FU, range 93–197 months). Quality of life and mood were evaluated using the SF36 and Beck Depression Index (BDI) questionnaires.ResultsPatients reached an improvement in motor symptoms of 63.8 ± 5.7% (mean ± SE) at ST-FU and 67.9 ± 6.1% at LT-FU. Moreover, a significant and stable reduction in disability was shown following DBS (54.2 ± 9.4% at ST-FU and 53.8 ± 9.2% at LT-FU). BDI and SF36 had improved by 40% and 23%, respectively, at LT-FU (n = 14). Stimulation-induced adverse events included swallowing difficulties, dysarthria, and bradykinesia. Pulse generator (n = 3) and electrodes (n = 5) were revised in seven patients due to infection.ConclusionsPallidal DBS is a safe and efficacious long-term treatment for dystonia with sustained effects on motor impairment and disability, accompanied by a robust improvement in mood and quality of life.

Functional and Structural Connectivity Patterns Associated with Clinical Outcomes in Deep Brain Stimulation of the Globus Pallidus Internus for Generalized Dystonia.

Deep brain stimulation is a well-established treatment for generalized dystonia, but outcomes remain variable. Establishment of an imaging marker to guide device targeting and programming could possibly impact the efficacy of deep brain stimulation in dystonia, particularly in the absence of acute clinical markers to indicate benefit. We hypothesize that the stimulation-based functional and structural connectivity using resting-state fMRI and DTI can predict therapeutic outcomes in patients with generalized dystonia and deep brain stimulation. We performed a retrospective analysis of 39 patients with inherited or idiopathic-isolated generalized dystonia who underwent bilateral globus pallidus internus deep brain stimulation. After electrode localization, the volumes of tissue activated were modeled and used as seed regions for functional and structural connectivity measures using a normative data base. Resulting connectivity maps were correlated with postoperative improvement in the Unified Dystonia Rating Scale score. Structural connectivity between the volumes of tissue activated and the primary sensorimotor cortex was correlated with Unified Dystonia Rating Scale improvement, while more anterior prefrontal connectivity was inversely correlated with Unified Dystonia Rating Scale improvement. Functional connectivity between the volumes of tissue activated and primary sensorimotor regions, motor thalamus, and cerebellum was most correlated with Unified Dystonia Rating Scale improvement; however, an inverse correlation with Unified Dystonia Rating Scale improvement was seen in the supplemental motor area and premotor cortex. Functional and structural connectivity with multiple nodes of the motor network is associated with motor improvement in patients with generalized dystonia undergoing deep brain stimulation. Results from this study may serve as a basis for future development of clinical markers to guide deep brain stimulation targeting and programming in dystonia.

Evaluation of a programming algorithm for deep brain stimulation in dystonia used in a double-blind, sham-controlled multicenter study

BackgroundProgramming deep brain stimulation in dystonia is difficult because of the delayed benefits and absence of evidence-based guidelines. Therefore, we evaluated the efficacy of a programming algorithm applied in a double-blind, sham-controlled multicenter study of pallidal deep brain stimulation in dystonia.MethodsA standardized monopolar review to identify the contact with the best acute antidystonic effect was applied in 40 patients, who were then programmed 0.5 V below the adverse effect threshold and maintained on these settings for at least 3 months, if tolerated. If no acute effects were observed, contact selection was based on adverse effects or anatomical criteria. Three-year follow-up data was available for 31 patients, and five-year data for 32 patients. The efficacy of the algorithm was based on changes in motor scores, adverse events, and the need for reprogramming.ResultsThe mean (±standard deviation) dystonia motor score decreased by 73 ± 24% at 3 years and 63 ± 38% at 5 years for contacts that exhibited acute improvement of dystonia (n = 17) during the monopolar review. Contacts without acute benefit improved by 58 ± 30% at 3 years (n = 63) and 53 ± 31% at 5 years (n = 59). Interestingly, acute worsening or induction of dystonia/dyskinesia (n = 9) correlated significantly with improvement after 3 years, but not 5 years.ConclusionsMonopolar review helped to detect the best therapeutic contact in approximately 30% of patients exhibiting acute modulation of dystonic symptoms. Acute improvement, as well as worsening of dystonia, predicted a good long-term outcome, while induction of phosphenes did not correlate with outcome.Trial registrationClinicalTrials.gov NCT00142259.

Microelectrode Neuronal Activity of the Internal Globus Pallidus in Dystonia Correlates with Postoperative Neuromodulation Effects and Placement of the Stimulation Electrode

BackgroundDeep brain stimulation (DBS) is emerging as a viable treatment option for selected patients with dystonia. Intraoperative extracellular microelectrode recordings (MER) are considered as the standard electrophysiological method for the precise positioning of the DBS electrode into the target brain structure. Accurate targeting of the permanent stimulation electrode into the Globus Pallidus internus (GPi) is key to positive long-term effects. The suitability of the location is peroperatively assessed by microelectrodes that register single-unit neuronal activity. The aim of this article is to analyse electrophysiological recordings of patient's neuronal activity with a focus on the identification of markers relevant to the patient's clinical state. MethodsIn this study, 13 patients chronically treated with double-sided DBS GPi were examined with a microrecording. The signal (24 kHz) processing, included bandpass filtering (0.5–5 kHz), automated detection of artefacts and feature extraction. Pre-processed signals were analysed by means of statistical learning. ResultsThe results show that the GPi was distinguished from its vicinity with p < 0.001 and 3 machine learning models AUCs had an accuracy of higher than 0.87. The observed biomarker, Hjort mobility, additionally correlated with the long-term neuromodulation effect (rho = −0.4; p < 0.05). Furthermore, we revealed a change of neural activity associated with the active distal DBS contact localization along the medio-lateral direction. ConclusionThis paper demonstrates the quantitative relationship between electrophysiological findings and the clinical effects of pallidal stimulation in dystonia and suggested objectification predictors of the effectiveness of this therapy.

Importance of the initial response to GPi deep brain stimulation in dystonia: A nine year quality of life study

BackgroundLong-term efficacy of deep brain stimulation (DBS) on health-related quality-of-life (HRQoL) for isolated dystonia is not well established. This study aims to determine the long-term impact of DBS on HRQoL outcomes and identify clinical predictors. MethodsWe retrospectively investigated 16 inherited or idiopathic isolated dystonia patients treated with bilateral globus pallidus internus DBS who were followed beyond 9 years at our center. The cohort consisted of 9 males, 7 females; 10 generalized, 6 segmental; mean (range) age at implantation, 37.0 (8–67) years; mean follow-up duration after implantation, 10.9 (9–13) years. We employed the Unified Dystonia Rating Scale for motor and Short Form Health Survey for HRQoL assessments to monitor the change longitudinally. We analyzed the changes in motor and HRQoL at 1–2 years (short-term) and ≥9 years (long-term) follow-up as compared to baseline with a Wilcoxon signed-rank test. We assessed the factors that predicted motor and HRQoL improvement with univariate regression analyses. ResultsMotor (41.6%; p = 0.004) and HRQoL (total score, p = 0.039) improvements remained significant at long-term follow-up and, in the regression analysis, change in HRQoL outcomes correlated significantly with change in motor outcomes (R2 = 0.384, p = 0.010). Additionally, short-term motor and HRQoL improvements predicted the long-term motor (R2 = 0.384, p = 0.010) and HRQoL (total score, R2 = 0.594, p < 0.001) outcomes, respectively. ConclusionMotor and HRQoL improvements with DBS in isolated dystonia remain sustained for nearly a decade and may largely be predictable by the short-term response to DBS.

Benefits of pallidal stimulation in dystonia are linked to cerebellar volume and cortical inhibition

Clinical benefits of pallidal deep brain stimulation (GPi DBS) in dystonia increase relatively slowly suggesting slow plastic processes in the motor network. Twenty-two patients with dystonia of various distribution and etiology treated by chronic GPi DBS and 22 healthy subjects were examined for short-latency intracortical inhibition of the motor cortex elicited by paired transcranial magnetic stimulation. The relationships between grey matter volume and intracortical inhibition considering the long-term clinical outcome and states of the GPi DBS were analysed. The acute effects of GPi DBS were associated with a shortening of the motor response whereas the grey matter of chronically treated patients with a better clinical outcome showed hypertrophy of the supplementary motor area and cerebellar vermis. In addition, the volume of the cerebellar hemispheres of patients correlated with the improvement of intracortical inhibition which was generally less effective in patients than in controls regardless of the DBS states. Importantly, good responders to GPi DBS showed a similar level of short-latency intracortical inhibition in the motor cortex as healthy controls whereas non-responders were unable to increase it. All these results support the multilevel impact of effective DBS on the motor networks in dystonia and suggest potential biomarkers of responsiveness to this treatment.

High frequency somatosensory stimulation in dystonia: Evidence fordefective inhibitory plasticity.

Apart from motor symptoms, multiple deficits of sensory processing have been demonstrated in dystonia. The most consistent behavioural measure of this is abnormal somatosensory temporal discrimination threshold, which has recently been associated with physiological measures of reduced inhibition within the primary somatosensory area. High-frequency repetitive sensory stimulation is a patterned electric stimulation applied to the skin through surface electrodes that has been recently reported to shorten somatosensory temporal discrimination in healthy subjects and to increase the resting level of excitability in several different types of inhibitory interaction in the somatosensory and even motor areas. We tested whether high-frequency repetitive sensory stimulation could augment cortical inhibition and, in turn, ameliorate somatosensory temporal discrimination in cervical dystonia. Somatosensory temporal discrimination and a number of electrophysiological measures of sensorimotor inhibition and facilitation were measured before and after 45 minutes of high-frequency repetitive sensory stimulation. As compared with a group of healthy volunteers of similar age, in whom high-frequency repetitive sensory stimulation increased inhibition and shortened somatosensory temporal discrimination, patients with cervical dystonia showed a consistent, paradoxical response: they had reduced suppression of paired-pulse somatosensory evoked potentials, as well as reduced high-frequency oscillations, lateral inhibition, and short interval intracortical inhibition. Somatosensory temporal discrimination deteriorated after the stimulation protocol, and correlated with reduced measures of inhibition within the primary somatosensory cortex. We suggest that patients with dystonia have abnormal homeostatic inhibitory plasticity within the sensorimotor cortex and that this is responsible for their paradoxical response to high-frequency repetitive sensory stimulation. © 2018 International Parkinson and Movement Disorder Society.

F60. Acute and chronic changes of motor network excitability in relation to the clinical benefit of pallidal stimulation in dystonia: A combined TMS and VBM study

Introduction Dystonia patients express less effective intracortical inhibition, which can potentially be restored with pallidal deep brain stimulation (DBS). The DBS-related clinical benefit in dystonia increases relatively slowly, suggesting an induction of slow plastic processes in regions involved with motor control. In our study, we explored the relationship between intracortical inhibition of the motor cortex, brain morphology, and DBS-related clinical effects. Methods Twenty-two patients (mean age 51 ± (SD)17 years) with dystonia of various distribution and etiology treated by chronic pallidal DBS and 22 healthy subjects were included in the study. Voxel-based morphometry of postoperative T1-weighted images (MPRAGE, 1 × 1 × 1 mm) was calculated for gray matter (GM) density in each voxel using CAT12/SPM12 software. Paired TMS with subthreshold conditioning stimulus followed by a supratreshold testing stimulus were applied to the motor cortex to elicit short-latency intracortical inhibition (SICI) of the motor evoked potential. The clinical effect of DBS was expressed as a change in the dystonic score (BFMDS or TWSTRS) between actual DBS ON condition and the preoperative state. Results Dystonia patients showed increased GM density in the supplementary motor area (SMA) and middle cingulate in comparison with healthy controls (p Conclusion Good responders to pallidal DBS treatment exhibited a similar level of SICI as healthy controls but non-responders were unable to increase it. Brain changes of treated patients possibly underwent grey matter rebuilding with cerebellar hypertrophy quantitatively related to the improvement of intracortical inhibition and with hypertrophy in the cortex involved in motor act preparation. All these results support the multilevel impact of effective DBS on motor networks in dystonia. Supported by the grants GACR 16-13323S.

F151. Sensorimotor cortex plasticity correlates with effectiveness of pallidal stimulation in dystonia

Introduction Deep brain stimulation (DBS) of the globus pallidus interna (GPi) is an effective symptomatic treatment of farmacoresistant dystonic syndromes. The sensorimotor cortex of dystonia patients exhibits an exaggerated responsiveness to the TMS (transcranial magnetic stimulation) in conditioning protocols. The aim of our study was to analyse the excitability of the primary motor cortex (MI) in relation to modulation of input from the primary somatosensory cortex (SI) in dystonia patients treated by GPi DBS. Methods We examined 21 patients (mean age 51 ± (SD)17 years) with dystonia treated by GPi DBS. The SI was modulated in DBS ON and OFF conditions by a 2-min series of paired associative stimulation (PAS) with 5 Hz frequency, consisting of electrical stimulation of the median nerve followed by 20 ms of subthreshold TMS pulse. The excitability of the MI was tested by motor evoked potentials (MEP) applied before and after the PAS. The clinical effect (CE) was expressed as a change in the dystonic score between DBS ON condition and the preoperative state. Results The SI PAS caused a decrease of the MEP amplitude in dystonia patients with the GPi DBS ON state in comparison with GPi DBS OFF state ( p p N = 8, p p N = 13, >25% CE) had the MEP amplitude unchanged after the SI PAS in both of the GPi DBS conditions. Conclusion The SI PAS intervention applied over SI cortex affected motor cortex excitability in dystonia patients but not in healthy controls. The GPi DBS reduced the sensorimotor cortex plasticity of dystonia patients under level seen in the GPi DBS off state and even under the level seen in healthy controls. Surprisingly, only poor responders to GPi DBS therapy showed a loss of an inhibitory effect of the SI on the MI immediately after switching stimulation off in comparison with good responders and healthy controls. This may suggest, that the GPi DBS normalizes the excitability of MI through strengthening of the sensorimotor interaction and causes long lasting cortical plasticity changes in good responders which may contribute to better suppression of the dystonic symptoms. Supported by the grants GACR 16-13323S, PROGRES Q27/LF1 and MJFF11362.

11-Clinical benefit of pallidal stimulation in dystonia is related to improved intracortical inhibition and local grey matter hypertrophy

Background Treatment efficacy of pallidal stimulation (GPi DBS) in dystonia varies and the benefit increases slowly, suggesting induction of slow plastic processes in regions involved with motor control. Methods We examined 19 patients (mean age 48 ± (SD)18 years) with cervical (N = 7) or generalized dystonia (N = 12) of various origin by chronic GPi DBS for 57 ± 28 months. Voxel-based morphometry of postoperative T1-weighted images was calculated for gray matter (GM) density in every patient and compared with 20 matched controls. Paired TMS was applied to the motor cortex to elicit short-latency intracortical inhibition (SICI) of the motor evoked potential. The clinical effect of GPi DBS was expressed as a change in the dystonic score (BFMDS or TWSTRS) between actual GPi DBS ON condition and the preoperative state. Results Dystonia patients showed increased GM density in the SMA and middle cingulate in comparison with healthy controls (p Conclusions Brain changes of chronically GPi DBS treated patients possibly reflect “hardwire” rebuilding of motor regions associated with functional improvement. Supported by the grant GACR 16-13323S.

Therapeutic Use of Non-invasive Brain Stimulation in Dystonia.

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive methods for stimulating cortical neurons that have been increasingly used in the neurology realm and in the neurosciences applied to movement disorders. In addition, these tools have the potential to be delivered as clinically therapeutic approach. Despite several studies support this hypothesis, there are several limitations related to the extreme variability of the stimulation protocols, clinical enrolment and variability of rTMS and tDCS after effects that make clinical interpretation very difficult. Aim of the present study will be to critically discuss the state of art therapeutically applications of rTMS and tDCS in dystonia.

Rechargeable or Nonrechargeable Deep Brain Stimulation in Dystonia: A Cost Analysis

Deep brain stimulation of the internal Globus Pallidus (GPi DBS) delivered by an implantable neurostimulator (INS) is an established, effective, and safe treatment option for patients with medically refractory primary dystonia. Compared to other DBS targets, the battery life of the INS is substantially shorter due to the higher energy demands required to penetrate the GPi resulting in faster battery depletion and more frequent hospitalizations for INS replacement. We, therefore, performed a cost analysis to compare a rechargeable DBS system, Activa®RC, with nonrechargeable systems, from the perspective of the French public health insurer. To estimate the cost of INS replacement in the nonrechargeable cohort, and costs potentially avoided in the hypothetical Activa® RC cohort, the medical records of patients who had undergone GPi DBS with a nonrechargeable INS between 1996 and 2010 at a center in France were accessed. Replacement rates were estimated for up to nine years. With Activa® RC, a total of 315 hospitalizations for replacement procedures would have been avoided over nine years compared with a nonrechargeable INS, resulting in a discounted mean direct medical cost per patient over nine years of €50,119 with a nonrechargeable INS and €33,306 with Activa® RC, a reduction of 34%. The adoption of a rechargeable instead of a nonrechargeable INS for eligible patients with dystonia may provide substantial savings to the public health insurer in France.

Intraoperative Thresholds for Capsular Stimulation Are Reliable for Chronic Pallidal Deep Brain Stimulation in Dystonia

Background: The threshold current for inducing muscle contractions by stimulation of pyramidal tract fibres adjacent to the globus pallidus internus (GPi) is, besides microelectrode recordings for the determination of nuclear boundaries, currently the only neurophysiological marker for intraoperative refinement of the anatomically planned target point for pallidal deep brain stimulation (GPi-DBS) in dystonia. Objectives: To determine the relationship between intraoperative thresholds for muscle contractions under general anaesthesia and postoperative thresholds in GPi-DBS. Methods: Intraoperatively, current amplitude thresholds (120 µs, 130 Hz) were determined in 6 dystonic patients under general anaesthesia (through the uninsulated tip of the microelectrode guide tube). Postoperative localization of chronic stimulation electrodes by MRI and image fusion with the stereotactic planning determined the stimulation contact for comparing thresholds with intraoperative values. Results: Current thresholds were 3.3 ± 0.8 mA intraoperatively (follow-up 0, FU0; n = 12), 2.9 ± 1.2 mA within 1 week after surgery (FU1; n = 12), and 3.5 ± 1.6 mA after 6-17 months (FU2; n = 8). FU0 and FU1 differed by trend, and FU1 and FU2 were significantly different (Friedman test, p = 0.0048; post hoc Dunn multiple comparison test, p < 0.05). FU0 and FU2 were not different. Discussion: The threshold amplitude to induce tonic muscular contractions may constitute a valid approach of functionally refining the anatomically guided electrode placement in GPi-DBS for dystonia, because intraoperative values are predictive for postoperative thresholds with the chronically implanted neurostimulation system.