DBS Programming Research Articles

348 An Integrated Solution to Predict the Stimulation Parameters After STN DBS for PD

Abstract INTRODUCTION Deep brain stimulation (DBS) titration is experience dependent and time consuming. It is expected to be more challenging with the wider use of directional DBS leads. Connectivity-based methods for stimulation titration are required. We hypothesized that stimulation parameters can be estimated based on the cortical connections of the DBS electrodes. METHODS Twenty-four Parkinson's disease (PD) patients with subthalamic nucleus (STN) DBS were included. All patients had preoperative 3T diffusion imaging (60 directions) and 1-yr follow-up after DBS. We recorded parameters associated with stimulation-induced acute clinical effects (ACE) during DBS programming. We classified them into improvement (rigidity, bradykinesia, and tremor) and side effects (paresthesia, motor contractions, visual disturbances). Using probabilistic tractography, we identified the cortical voxels uniquely associated with each ACE category. A prediction algorithm, based on support vector machines (SVM) with repeated cross-validation, was trained on the unique features of cortical connectivity. This algorithm was then used to estimate the optimal contact and stimulation amplitude combination for each DBS contact in both hemispheres. A blinded comparison with actual stimulation parameters was done using sensitivity analysis. We also tested the classifier on another independent cohort of 14 PD patients with STN DBS. RESULTS Clusters in premotor and SMA (area 6) were significantly associated with therapeutic stimulation. At 1 yr, 42 of the 47 stimulation electrodes were accurately estimated as “efficacious” and the therapeutic window calculated to be = 3 V in 31(66%) and between 2 and 2.9 V in 11(24%), respectively. The SVM algorithm had excellent sensitivity (area under curve = 0.8506, 95% confidence interval 0.7026-0.9987). Its sensitivity was maintained in the validation cohort. CONCLUSION The optimal stimulation settings after DBS can be estimated from the pattern of cortical connections of each electrode. Prospective validation in a larger cohort may help test the prediction accuracy of this approach.

Deep brain stimulation for intractable neuropathic facial pain.

OBJECTIVE Deep brain stimulation (DBS) is a well-established, evidence-based therapy with FDA approval for Parkinson's disease and essential tremor. Despite the early successful use of DBS to target the sensory thalamus for intractable facial pain, subsequent studies pursuing various chronic pain syndromes reported variable efficacy, keeping DBS for pain as an investigational and "off-label" use. The authors report promising results for a contemporary series of patients with intractable facial pain who were treated with DBS. METHODS Pain outcomes for 7 consecutive patients with unilateral, intractable facial pain undergoing DBS of the ventral posteromedial nucleus of the thalamus (VPM) and the periaqueductal gray (PAG) were retrospectively reviewed. Pain was assessed preoperatively and at multiple postoperative time points using the visual analog scale (VAS), the Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2), and the Pain Disability Index (PDI). RESULTS VAS scores significantly decreased from a mean ± SD of 9.0 ± 1.3 preoperatively to 2.6 ± 1.5 at 1 year postoperatively (p = 0.001). PDI scores decreased from a mean total of 48.5 to 28.5 (p = 0.01). SF-MPQ-2 scores decreased from a mean of 4.6 to 2.4 (p = 0.03). Notably, several patients did not experience maximum improvement until 6-9 months postoperatively, correlating with repeated programming adjustments. CONCLUSIONS DBS of the VPM and PAG is a potential therapeutic option for patients suffering from severe, intractable facial pain refractory to other interventions. Improved efficacy may be observed over time with close follow-up and active DBS programming adjustments.

The impact of subthalamic deep brain stimulation on polysomnographic sleep pattern in patients with Parkinson's disease – Preliminary report

Aim of the studyWe present the preliminary results of the study focused on the impact of subthalamic deep brain stimulation (DBS-STN) on sleep and other non-motor symptoms (NMS). Materials and methodsTen patients with advanced PD, underwent two-night polysomnography (PSG) mean 1.1 week before surgery and 6.2 months post DBS programming. NMS were assessed with a set of scales before surgery and 6 months and 12 months following DBS programming. ResultsContrary to previous studies, we noted deterioration of sleep pattern in the follow-up PSG. We found a decrease in total sleep time, duration of the stage N2, with prolongation of stage N1 and wakefulness after sleep onset. We did not detect any impact of DBS-STN on subjective severity of restless legs syndrome. REM – sleep behavior disorder, however reported was not observed in any patient during PSG evaluations. We also found statistically significant correlations between severity of sleep disturbances and quality of life, as well as, between severity of motor symptoms and worse objective sleep quality. ConclusionsWe found that DBS-STN improved quality of life, subjective quality of sleep and sleepiness, however, contrary to the previous studies the objective parameters of sleep worsened after the surgery.

Anatomical Correlates of Uncontrollable Laughter With Unilateral Subthalamic Deep Brain Stimulation in Parkinson’s Disease

Subthalamic nucleus deep brain stimulation (STN-DBS) is a well-established treatment for the management of motor complications in Parkinson's disease. Uncontrollable laughter has been reported as a rare side effect of STN stimulation. The precise mechanism responsible for this unique phenomenon remains unclear. We examined in detail the DBS electrode position and stimulation parameters in two patients with uncontrollable laughter during programming after STN-DBS surgery and illustrated the anatomical correlates of the acute mood changes with STN stimulation. Unilateral STN-DBS induced uncontrollable laughter with activation of the most ventral contacts in both patients. However, the location of the electrodes responsible for this adverse effect differed between the patients. In the first patient, the DBS lead was placed more inferiorly and medially within the STN. In the second patient, the DBS lead was implanted more anteriorly and inferiorly than initially planned at the level of the substantia nigra reticulata (SNr). Unilateral STN-DBS can induce acute uncontrollable laughter with activation of electrodes located more anterior, medial, and inferior in relationship with the standard stereotactic STN target. We suggest that simulation of ventral and medial STN, surrounding limbic structures or the SNr, is the most plausible anatomical substrate responsible for this acute mood and behavioral change. Our findings provide insight into the complex functional neuroanatomical relationship of the STN and adjacent structures important for mood and behavior. DBS programming with more dorsal and lateral contacts within the STN should be entertained to minimize the emotional side effects.

Dysarthria in pallidal Deep Brain Stimulation in dystonia depends on the posterior location of active electrode contacts: a pilot study

BackgroundPallidal Deep Brain Stimulation (GPi-DBS) is an efficient treatment for primary dystonia. We investigated stimulation-induced dysarthria, which is the most frequent side-effect of GPi-DBS. MethodsSpeech was recorded while reading a standard text, and performing rapid syllable repetitions ON and OFF DBS in ten dystonia patients (6 men; 3 cervical, 4 segmental, 3 generalized, unselected for DBS-related speech impairments). Speech and articulation rate, pauses, and syllable repetition rates were extracted via acoustic analysis. Locations of active stimulation contacts and volumes of tissue activated (VTA) were calculated. ResultsThe number of pauses increased significantly ON vs. OFF stimulation (Wilcoxon test, p < 0.05). More posteriorly localized active contacts were associated with slower syllable repetition (Pearson correlation, p < 0.05). VTA size did not correlate with any measure of dysarthria. ConclusionUsing quantitative acoustic signal analysis, this study demonstrates that GPi-DBS alters motor aspects of speech. Both inadvertent stimulation of parts of the internal capsule, or interference with GPi function and outflow are possible causes. Understanding causes of GPi-DBS-induced speech changes can improve DBS programming.

Intraoperative clinical testing overestimates the therapeutic window of the permanent DBS electrode in the subthalamic nucleus

Intraoperative test stimulation is established to optimize target localization in STN DBS, but requires a time-consuming awake surgery in off-medication state. The aim of this study was to compare the thresholds of stimulation-induced effects of test stimulation and the permanent electrode. Fifty-nine PD patients receiving bilateral STN DBS were clinically examined with stepwise increasing monopolar stimulation during surgery and DBS programming at matched stimulation depths. Thresholds of therapeutic and side effects were obtained from standardized examination protocols. Postoperative stimulation via the permanent electrode caused side effects at a significantly lower threshold than predicted during intraoperative test stimulation (P<0.001); whereas sufficient therapeutic effects were achieved at significantly higher thresholds (P<0.001). Intraoperative testing may lead to an overestimation of the therapeutic window. The two different electrodes lead to distinct spreading of the electric field in the STN and surrounding tissues that causes different volume of tissue activated (VTA). Clinicians involved in DBS surgery and programming should be aware of the differences in both stimulation settings, concerning electrodes geometry, stimulation modes as well as the impact of time. Therapeutic and side effects of permanent stimulation are not predictable by intraoperative test stimulation. Test stimulation may be an orientating test for very low thresholds of side effects instead.

Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: The Effect of Varying Stimulation Parameters.

Subthalamic Nucleus Deep Brain Stimulation (STN DBS) is a well-established and effective treatment modality for selected patients with Parkinson’s disease (PD). Since its advent, systematic exploration of the effect of stimulation parameters including the stimulation intensity, frequency, and pulse width have been carried out to establish optimal therapeutic ranges. This review examines published data on these stimulation parameters in terms of efficacy of treatment and adverse effects. Altering stimulation intensity is the mainstay of titration in DBS programming via alterations in voltage or current settings, and is characterised by a lower efficacy threshold and a higher side effect threshold which define the therapeutic window. In addition, much work has been done in exploring the effects of frequency modulation, which may help patients with gait freezing and other axial symptoms. However, there is a paucity of data on the use of ultra-short pulse width settings which are now possible with technological advances. We also discuss current evidence for the use of novel programming techniques including directional and adaptive stimulation, and highlight areas for future research.

The Seven Dirty Words YouCan Say on Cable and DBS: Extending BroadcastIndecency Regulation and the First Amendment

Congress has recently considered legislation that would increase the penalties for the broadcast of indecent content and extend broadcast indecency regulation to cable and direct broadcast satellite. Under existing case law this extension of indecency regulation likely would be unconstitutional for two primary reasons. First, many of the factors that justify broadcast indecency regulation are not present in cable or DBS. Second, both cable and DBS can provide subscribers with the ability to block unwanted programming, which would likely be found by courts to be a less restrictive way for the government to achieve its interest in protecting children from exposure to indecent cable or DBS programming.

The Canadian multicenter trial of pallidal deep brain stimulation for cervical dystonia: preliminary results in three patients

Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is beneficial for generalized dystonia and has been proposed as a treatment for cervical dystonia. The Canadian Stereotactic/Functional and Movement Disorders Groups designed a pilot project to investigate the following hypothesis: that bilateral DBS of the GPi will reduce the severity of cervical dystonia at 1 year of follow up, as scored in a blinded fashion by two neurologists using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Secondary outcome measures included pain and disability subscores of the TWSTRS, Short Form-36 quality of life index, and the Beck Depression Inventory. Three patients have undergone surgery in Calgary with a follow-up duration of 7.4 +/- 5.9 months (mean +/- standard deviation). One patient underwent inadvertent ineffective stimulation for the first 3 months and did not experience a benefit until DBS programming was corrected. All three patients had rapid response to stimulation, with the muscles relaxing immediately and abnormal movements improving within days. Total TWSTRS scores improved by 79%, and severity subscores improved significantly, from 15.7 +/- 2.1 to 7.7 +/- 2.9 (paired t-test, p = 0.02). Pain and disability subscores improved from 25.5 +/- 4.1 to 3.3 +/- 3.1 (paired t-test, p = 0.002) and from 13.3 +/- 4.9 to 3.3 +/- 4.2 (paired t-test, p = 0.06), respectively. Although it is too early to reach broad conclusions, this report of preliminary results confirms the efficacy of DBS of the GPi for cervical dystonia.