Linking connectivity of deep brain stimulation of nucleus accumbens area with clinical depression improvements: a retrospective longitudinal case series.

Treatment-resistant depression is a severe form of major depressive disorder and deep brain stimulation is currently an investigational treatment. The stimulation's therapeutic effect may be explained through the functional and structural connectivities between the stimulated area and other brain regions, or to depression-associated networks. In this longitudinal, retrospective study, four female patients with treatment-resistant depression were implanted for stimulation in the nucleus accumbens area at our center. We analyzed the structural and functional connectivity of the stimulation area: the structural connectivity was investigated with probabilistic tractography; the functional connectivity was estimated by combining patient-specific stimulation volumes and a normative functional connectome. These structural and functional connectivity profiles were then related to four clinical outcome scores. At 1-year follow-up, the remission rate was 66%. We observed a consistent structural connectivity to Brodmann area 25 in the patient with the longest remission phase. The functional connectivity analysis resulted in patient-specific R-maps describing brain areas significantly correlated with symptom improvement in this patient, notably the prefrontal cortex. But the connectivity analysis was mixed across patients, calling for confirmation in a larger cohort and over longer time periods.

Programming of subthalamic nucleus deep brain stimulation with hyperdirect pathway and corticospinal tract-guided parameter suggestions.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease. Stimulation of the hyperdirect pathway (HDP) may mediate the beneficial effects, whereas stimulation of the corticospinal tract (CST) mediates capsular side effects. The study's objective was to suggest stimulation parameters based on the activation of the HDP and CST. This retrospective study included 20 Parkinson's disease patients with bilateral STN DBS. Patient-specific whole-brain probabilistic tractography was performed to extract the HDP and CST. Stimulation parameters from monopolar reviews were used to estimate volumes of tissue activated and to determine the streamlines of the pathways inside these volumes. The activated streamlines were related to the clinical observations. Two models were computed, one for the HDP to estimate effect thresholds and one for the CST to estimate capsular side effect thresholds. In a leave-one-subject-out cross-validation, the models were used to suggest stimulation parameters. The models indicated an activation of 50% of the HDP at effect threshold, and 4% of the CST at capsular side effect threshold. The suggestions for best and worst levels were significantly better than random suggestions. Finally, we compared the suggested stimulation thresholds with those from the monopolar reviews. The median suggestion errors for the effect threshold and side effect threshold were 1 and 1.5 mA, respectively. Our stimulation models of the HDP and CST suggested STN DBS settings. Prospective clinical studies are warranted to optimize tract-guided DBS programming. Together with other modalities, these may allow for assisted STN DBS programming.

Probabilistic Mapping Reveals Optimal Stimulation Site in Essential Tremor.

OBJECTIVE: The objective of this study was to obtain individual clinical and neuroimaging data of patients undergoing deep brain stimulation (DBS) for essential tremor (ET) from 5 different European centers to identify predictors of outcome and to identify an optimal stimulation site. METHODS: We analyzed retrospectively baseline covariates, pre- and postoperative clinical tremor scores (for 12 months) as well as individual imaging data from 119 patients to obtain individual electrode positions and stimulation volumes. Individual imaging and clinical data were used to calculate a probabilistic stimulation map in normalized space using voxel-wise statistical analysis. Finally, we used this map to train a classifier to predict tremor improvement. RESULTS: Probabilistic mapping of stimulation effects yielded a statistically significant cluster that was associated with a tremor improvement >50%. This cluster of optimal stimulation extended from the posterior subthalamic area to the ventralis intermedius nucleus and coincided with a normative structural connectivity-based cerebellothalamic tract (CTT). The combined features "distance between the stimulation volume and the significant cluster" and "CTT activation" were used as a predictor of tremor improvement. This correctly classified a >50% tremor improvement with a sensitivity of 89% and a specificity of 57%. INTERPRETATION: Our multicenter ET probabilistic stimulation map identified an area of optimal stimulation along the course of the CTT. The results of this study are mainly descriptive until confirmed in independent datasets, ideally through prospective testing. This target will be made openly available and may be used to guide surgical planning and for computer-assisted programming of DBS in the future. ANN NEUROL 2022;91:602-612.

Spectral Topography of the Subthalamic Nucleus to Inform Next-Generation Deep Brain Stimulation.

BACKGROUND: The landscape of neurophysiological symptoms and behavioral biomarkers in basal ganglia signals for movement disorders is expanding. The clinical translation of sensing-based deep brain stimulation (DBS) also requires a thorough understanding of the anatomical organization of spectral biomarkers within the subthalamic nucleus (STN). OBJECTIVES: The aims were to systematically investigate the spectral topography, including a wide range of sub-bands in STN local field potentials (LFP) of Parkinson's disease (PD) patients, and to evaluate its predictive performance for clinical response to DBS. METHODS: STN-LFPs were recorded from 70 PD patients (130 hemispheres) awake and at rest using multicontact DBS electrodes. A comprehensive spatial characterization, including hot spot localization and focality estimation, was performed for multiple sub-bands (delta, theta, alpha, low-beta, high-beta, low-gamma, high-gamma, and fast-gamma (FG) as well as low- and fast high-frequency oscillations [HFO]) and compared to the clinical hot spot for rigidity response to DBS. A spectral biomarker map was established and used to predict the clinical response to DBS. RESULTS: The STN shows a heterogeneous topographic distribution of different spectral biomarkers, with the strongest segregation in the inferior-superior axis. Relative to the superiorly localized beta hot spot, HFOs (FG, slow HFO) were localized up to 2 mm more inferiorly. Beta oscillations are spatially more spread compared to other sub-bands. Both the spatial proximity of contacts to the beta hot spot and the distance to higher-frequency hot spots were predictive for the best rigidity response to DBS. CONCLUSIONS: The spatial segregation and properties of spectral biomarkers within the DBS target structure can additionally be informative for the implementation of next-generation sensing-based DBS. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Intraoperative Motor Evoked Responses to Double-Train Paradigm Stimulation for Guiding Lead Placement and Postoperative Programming in Spinal Cord Stimulation for Pain.

OBJECTIVE: We aimed to demonstrate the feasibility of using motor evoked responses to intraoperative double-train stimulation to guide lead placement and matching of intraoperative contacts with postoperative electrode programming in spinal cord stimulation for pain performed under general anesthesia. MATERIALS AND METHODS: The study included a series of 20 consecutive patients with refractory pain operated on under general anesthesia. Either percutaneous or paddle leads were implanted and positioned according to the intraoperative mapping results. Neurophysiologic mapping was performed with a double-train stimulation paradigm (intertrain interval of 60 milliseconds, three to five cathodal pulses with 0.5-millisecond pulse duration, and within-train interstimulus intervals of 2-4 milliseconds). The sites where dorsal column responses of the targeted dermatomes were detected were considered optimal for lead placement (intraoperative best contacts). Following spinal cord stimulator (SCS) lead placement, blinded postoperative programming of electrode contacts was matched with the intraoperative best contacts and the pain-paresthesia overlap for the trial phase. A binominal test was used as a statistical method; pre- and postoperative numeric rating scale (NRS) after three months was obtained. RESULTS: A total of 15 patients underwent spinal cord stimulation trial for intractable pain. Of these, ten patients (66%) had a successful trial and received permanent implants; one patient had a successful trial but was never intended to be implanted because of her poor health condition; four patients (26%) had an unsuccessful trial, leading to trial electrode explantation; and five patients had already had an implant with percutaneous leads and therefore underwent electrode revision, of whom four patients received paddle leads. In 18 of the 20 operated patients (90%), we found a match between the best intraoperative contacts and the postoperatively programmed contacts (significantly better than chance, p = 8.2 × 10-15). In 90% of the patients, a pain-paresthesia overlap of 100% was found. In the remaining two patients (10%), the postoperatively best programmed contacts were one contact away from the intraoperative neurophysiologic best contact. A mean preoperative NRS score of 8.2 (variance) and a mean follow-up NRS score after three months of 3.6 (variance) were obtained for all patients with implants. CONCLUSION: In this proof-of-concept study, we were able to demonstrate that SCS lead placement using a double-train stimulation paradigm performed under general anesthesia is a safe and feasible technique, offering reliable prediction of contacts for postoperative programming and excellent pain-paresthesia coverage.

Intraoperative Neurophysiological Monitoring During Spinal Cord Stimulation Surgery: A Systematic Review.

OBJECTIVES: This study aims to describe the state of literature regarding the use of intraoperative neurophysiological monitoring (IONM) during spinal cord stimulator surgery. MATERIALS AND METHODS: A systematic review of the use of IONM during spinal cord stimulation (SCS) surgery was performed using the following three data bases: PubMed, Ovid MEDLINE, and Embase. Research techniques included systematic research following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol by Cochrane, and backward searching. Qualitative analysis of included articles was performed using the methodologic index for nonrandomized studies assessment tool. Direction of effect, consistency across studies, and cost-effectiveness were narratively synthesized. RESULTS: A total of 15 records were identified through data base searching. All records used IONM methods under general anesthesia for guidance of epidural lead placement. IONM techniques used for determining lateralization in the found articles were compound muscle action potentials (CMAPs) (n = 8), somatosensory evoked potentials (SSEPs) (n = 3) or both (n = 4). Motor evoked potentials were used in three trials for neuroprotection purposes. Two studies were comparative, and 12 were noncomparative. CONCLUSIONS: We found a good body of level II evidence that using IONM during SCS surgery is a valid alternative to awake surgery and may even be superior regarding pain management, cost-effectiveness, and postoperative neurologic deficits. In direct comparison, the found evidence suggested using CMAP provided more consistently favorable results than using SSEP for midline placement of epidural leads under general anesthesia. Selection of IONM modality should be made on the basis of pathophysiology of disease, individual IONM experience, and the individual patient.

Deep Brain Stimulation of the Central Lateral and Ventral Posterior Thalamus for Central Poststroke Pain Syndrome: Preliminary Experience.

OBJECTIVE: The beneficial effects of thalamic deep brain stimulation (DBS) at various target sites in treating chronic central neuropathic pain (CPSP) remain unclear. This study aimed to evaluate the effectiveness of DBS at a previously untested target site in the central lateral (CL) thalamus, together with classical sensory thalamic stimulation (ventral posterior [VP] complex). MATERIALS AND METHODS: We performed a monocentric retrospective study of a consecutive series of six patients with CPSP who underwent combined DBS lead implantation of the CL and VP. Patient-reported outcome measures were recorded before and after surgery using the numeric rating scale (NRS), short-form McGill pain questionnaire (sf-MPQ), EuroQol 5-D quality-of-life questionnaire, and Beck Depression Inventory. DBS leads were reconstructed and projected onto a three-dimensional stereotactic atlas. RESULTS: NRS-but not sf-MPQ-rated pain intensity-was significantly reduced throughout the follow-up period of 12 months compared with baseline (p = 0.005, and p = 0.06 respectively, Friedman test). At the last available follow-up (12 to 30 months), three patients described a more than 50% reduction. Two of the three long-term responders were stimulated in the CL (1000 Hz, 90 µs, 3.5-5.0 mA), whereas the third preferred VP complex stimulation (50 Hz, 200 µs, 0.7-1.2 mA). No persistent procedure- or stimulation-associated side effects were noted. CONCLUSIONS: These preliminary findings suggest that DBS of the CL might constitute a promising alternative target in cases in which classical VP complex stimulation does not yield satisfactory postoperative pain reduction. The results need to be confirmed in larger, prospective series of patients.

Probabilistic Subthalamic Nucleus Stimulation Sweet Spot Integration Into a Commercial Deep Brain Stimulation Programming Software Can Predict Effective Stimulation Parameters.

OBJECTIVES: Subthalamic nucleus (STN) deep brain stimulation (DBS) programming in patients with Parkinson disease (PD) may be challenging, especially when using segmented leads. In this study, we integrated a previously validated probabilistic STN sweet spot into a commercially available software to evaluate its predictive value for clinically effective DBS programming. MATERIALS AND METHODS: A total of 14 patients with PD undergoing bilateral STN DBS with segmented leads were included. A nonlinear co-registration of a previously defined probabilistic sweet spot onto the manually segmented STN was performed together with lead reconstruction and tractography of the corticospinal tract (CST) in each patient. Contacts were ranked (level and direction), and corresponding effect and side-effect thresholds were predicted based on the overlap of the volume of activated tissue (VTA) with the sweet spot and CST. Image-based findings were correlated with postoperative clinical testing results during monopolar contact review and chronic stimulation parameter settings used after 12 months. RESULTS: Image-based contact prediction showed high interrater reliability (Cohen kappa 0.851-0.91). Image-based and clinical ranking of the most efficient ring level and direction of stimulation were matched in 72% (95% CI 57.0-83.3) and 65% (95% CI 44.9-81.2), respectively, across the whole cohort. The mean difference between the predicted and clinically observed effect thresholds was 0.79 ± 0.69 mA (p = 0.72). The median difference between the predicted and clinically observed side-effect thresholds was -0.5 mA (p < 0.001, Wilcoxon paired signed rank test). CONCLUSIONS: Integration of a probabilistic STN functional sweet spot into a surgical programming software shows a promising capability to predict the best level and directional contact(s) as well as stimulation settings in DBS for PD and could be used to optimize programming with segmented lead technology. This integrated image-based programming approach still needs to be evaluated on a bigger data set and in a future prospective multicenter cohort.

Combining Multimodal Biomarkers to Guide Deep Brain Stimulation Programming in Parkinson Disease.

BACKGROUND: Deep brain stimulation (DBS) programming of multicontact DBS leads relies on a very time-consuming manual screening procedure, and strategies to speed up this process are needed. Beta activity in subthalamic nucleus (STN) local field potentials (LFP) has been suggested as a promising marker to index optimal stimulation contacts in patients with Parkinson disease. OBJECTIVE: In this study, we investigate the advantage of algorithmic selection and combination of multiple resting and movement state features from STN LFPs and imaging markers to predict three relevant clinical DBS parameters (clinical efficacy, therapeutic window, side-effect threshold). MATERIALS AND METHODS: STN LFPs were recorded at rest and during voluntary movements from multicontact DBS leads in 27 hemispheres. Resting- and movement-state features from multiple frequency bands (alpha, low beta, high beta, gamma, fast gamma, high frequency oscillations [HFO]) were used to predict the clinical outcome parameters. Subanalyses included an anatomical stimulation sweet spot as an additional feature. RESULTS: Both resting- and movement-state features contributed to the prediction, with resting (fast) gamma activity, resting/movement-modulated beta activity, and movement-modulated HFO being most predictive. With the proposed algorithm, the best stimulation contact for the three clinical outcome parameters can be identified with a probability of almost 90% after considering half of the DBS lead contacts, and it outperforms the use of beta activity as single marker. The combination of electrophysiological and imaging markers can further improve the prediction. CONCLUSION: LFP-guided DBS programming based on algorithmic selection and combination of multiple electrophysiological and imaging markers can be an efficient approach to improve the clinical routine and outcome of DBS patients.

A prospective international multi-center study on safety and efficacy of deep brain stimulation for resistant obsessive-compulsive disorder.

Deep brain stimulation (DBS) has been proposed for severe, chronic, treatment-refractory obsessive-compulsive disorder (OCD) patients. Although serious adverse events can occur, only a few studies report on the safety profile of DBS for psychiatric disorders. In a prospective, open-label, interventional multi-center study, we examined the safety and efficacy of electrical stimulation in 30 patients with DBS electrodes bilaterally implanted in the anterior limb of the internal capsule. Safety, efficacy, and functionality assessments were performed at 3, 6, and 12 months post implant. An independent Clinical Events Committee classified and coded all adverse events (AEs) according to EN ISO14155:2011. All patients experienced AEs (195 in total), with the majority of these being mild (52% of all AEs) or moderate (37%). Median time to resolution was 22 days for all AEs and the etiology with the highest AE incidence was 'programming/stimulation' (in 26 patients), followed by 'New illness, injury, condition' (13 patients) and 'pre-existing condition, worsening or exacerbation' (11 patients). Sixteen patients reported a total of 36 serious AEs (eight of them in one single patient), mainly transient anxiety and affective symptoms worsening (20 SAEs). Regarding efficacy measures, Y-BOCS reduction was 42% at 12 months and the responder rate was 60%. Improvements in GAF, CGI, and EuroQol-5D index scores were also observed. In sum, although some severe AEs occurred, most AEs were mild or moderate, transient and related to programming/stimulation and tended to resolve by adjustment of stimulation. In a severely treatment-resistant population, this open-label study supports that the potential benefits outweigh the potential risks of DBS.

Electrical Stimulation for Cerebral Vasospasm After Subarachnoid Hemorrhage: A Systematic Review.

OBJECTIVES: Cerebral vasospasm is a severe and potentially lethal complication in patients with subarachnoid hemorrhage (SAH). Its pathogenesis is still not completely understood. The efficacy of current treatments, such as triple-H therapy or calcium channel blockers, is unsatisfactory, and a new therapy model would therefore be valuable. Electrical stimulation may have a considerable influence on cerebrovascular innervation. This systematic review gives an overview of the studies that have applied electrical stimulation in models of cerebral vasospasm. MATERIALS AND METHODS: We performed a systematic review of the literature, searching PubMed and Ovid Embase with the keywords "electric stimulation," "cerebral vasospasm," "subarachnoid hemorrhage," "sympathetic," and "parasympathetic." Additional papers were identified from the reference lists of the articles identified in the literature search. RESULTS: Increased cerebral blood flow (CBF) is a widely observed effect of spinal cord stimulation and sphenopalatine ganglion stimulation in models of physiological conditions or experimental cerebral vasospasm. Most studies were conducted in animals, 15 under physiological conditions and 11 in animals with SAH. Eight studies in humans were identified that examined the stimulation effect on CBF under physiological conditions. Only two studies looked at patients after SAH: one applied spinal cord stimulation (SCS) and the other transcutaneous electrical neurostimulation. Different mechanisms leading to stimulation-induced CBF increase that were discussed included "reversible functional sympathectomy," activation of brainstem vasomotor centers, involvement of central ascending pathways, release of neurohumoral factors, and interaction with sympathetic, parasympathetic, and trigeminal innervation. The results indicate that electrical stimulation is a promising procedure for prevention and treatment of cerebral vasospasm. CONCLUSION: Electrical stimulation, especially SCS and sphenopalatine ganglion stimulation, is a promising adjunct for existing therapies for vasospasm after SAH. Further experiments and prospective clinical studies are needed to establish its potential usefulness as a therapy or prevention option.

Proactive inhibition is not modified by deep brain stimulation for Parkinson's disease: An electrical neuroimaging study.

In predictable contexts, motor inhibitory control can be deployed before the actual need for response suppression. The brain functional underpinnings of proactive inhibition, and notably the role of basal ganglia, are not entirely identified. We investigated the effects of deep brain stimulation of the subthalamic nucleus or internal globus pallidus on proactive inhibition in patients with Parkinson's disease. They completed a cued go/no-go proactive inhibition task ON and (unilateral) OFF stimulation while EEG was recorded. We found no behavioural effect of either subthalamic nucleus or internal globus pallidus deep brain stimulation on proactive inhibition, despite a general improvement of motor performance with subthalamic nucleus stimulation. In the non-operated and subthalamic nucleus group, we identified periods of topographic EEG modulation by the level of proactive inhibition. In the subthalamic nucleus group, source estimation analysis suggested the initial involvement of bilateral frontal and occipital areas, followed by a right lateralized fronto-basal network, and finally of right premotor and left parietal regions. Our results confirm the overall preservation of proactive inhibition capacities in both subthalamic nucleus and internal globus pallidus deep brain stimulation, and suggest a partly segregated network for proactive inhibition, with a preferential recruitment of the indirect pathway.

Deep Brain Stimulation for Chronic Cluster Headache: Meta-Analysis of Individual Patient Data.

OBJECTIVE: Deep brain stimulation (DBS) is a treatment option for refractory chronic cluster headache (CCH). Despite several recent prospective case series reporting a good outcome, the effectiveness and the optimal stimulation target of DBS for CCH remain unclear. We aimed to obtain precise estimates and predictors of long-term pain relief in an individual patient data meta-analysis. Furthermore, we aimed to construct a probabilistic stimulation map of effective DBS. METHODS: We invited investigators of published cohorts of patients undergoing DBS for CCH, identified by a systematic review of MEDLINE from inception to Febuary 15, 2019, to provide individual patient data on baseline covariates, pre- and postoperative headache scores at median (12-month) and long-term follow-up, in addition to individual imaging data to obtain individual electrode positions. We calculated a stimulation map using voxel-wise statistical analysis. We used multiple regression analysis to estimate predictors of pain relief. RESULTS: Among 40 patients from four different cohorts representing ~50% of all previously published cases, we found a significant 77% mean reduction in headache attack frequency over a mean follow-up of 44 months, with an overall response rate of 75%. Positive outcome was not associated with baseline covariates. We identified 2 hotspots of stimulation covering the midbrain ventral and retrorubral tegmentum. INTERPRETATION: This study supports the hypothesis that DBS provides long-term pain relief for the majority of CCH patients. Our stimulation map of the region of influence of therapeutic DBS identified an optimal anatomical target site that can help surgeons to guide their surgical planning in the future. ANN NEUROL 2020;88:956-969.

Subthalamic nucleus activity dynamics and limb movement prediction in Parkinson's disease.

Whilst exaggerated bursts of beta frequency band oscillatory synchronization in the subthalamic nucleus have been associated with motor impairment in Parkinson's disease, a plausible mechanism linking the two phenomena has been lacking. Here we test the hypothesis that increased synchronization denoted by beta bursting might compromise information coding capacity in basal ganglia networks. To this end we recorded local field potential activity in the subthalamic nucleus of 18 patients with Parkinson's disease as they executed cued upper and lower limb movements. We used the accuracy of local field potential-based classification of the limb to be moved on each trial as an index of the information held by the system with respect to intended action. Machine learning using the naïve Bayes conditional probability model was used for classification. Local field potential dynamics allowed accurate prediction of intended movements well ahead of their execution, with an area under the receiver operator characteristic curve of 0.80 ± 0.04 before imperative cues when the demanded action was known ahead of time. The presence of bursts of local field potential activity in the alpha, and even more so, in the beta frequency band significantly compromised the prediction of the limb to be moved. We conclude that low frequency bursts, particularly those in the beta band, restrict the capacity of the basal ganglia system to encode physiologically relevant information about intended actions. The current findings are also important as they suggest that local subthalamic activity may potentially be decoded to enable effector selection, in addition to force control in restorative brain-machine interface applications.

Stereotactic biopsies of brainstem lesions: which approach?

BACKGROUND: Stereotactic biopsies for brainstem lesions are frequently performed to yield an accurate diagnosis and help guide subsequent management. In this study, we summarize our experience with different stereotactic approaches to brainstem lesions of different locations and discuss possible implications for safety and diagnostic yield. METHODS: We retrospectively analyzed 23 adult patients who underwent a stereotactic biopsy for brainstem lesions between October 2011 and December 2019. Depending on the location supra- or infratentorial, trajectories were planned. We assessed the postoperative complications during the hospital stay as well as the diagnostic yield. RESULTS: A supratentorial transfrontal approach was used in 16 (70%) cases, predominantly for lesions in the midbrain, upper pons, and medulla oblongata. An infratentorial, transcerebellar-transpeduncular approach was used in 7 (30%) cases mainly for lesions within the lower pons. All biopsies were confirmed to represent pathological tissue and a definitive diagnosis was achieved in 21 cases (91%). Three patients (13%) had transient weakness in the contralateral part of the body in the immediate postoperative period, which improved spontaneously. There was no permanent morbidity or mortality in this series of patients. CONCLUSION: Lesions of various locations within the brainstem can be successfully targeted via either a supratentorial transfrontal or an infratentorial transcerebellar transpeduncular approach. Our high diagnostic yield of over 90% and the low rate of complications underlines the diagnostic importance of this procedure in order to guide the medical management of these patients.

Stereotactic posterior midline approach under direct microscopic view for biopsy of medulla oblongata tumors: technical considerations.

BACKGROUND: Open and stereotactic transfrontal or transcerebellar approaches have been used to biopsy brainstem lesions. METHOD: In this report, a stereotactic posterior and midline approach to the distal medulla oblongata under microscopic view is described. The potential advantages and limitations are discussed, especially bilateral damage of the X nerve nuclei. CONCLUSION: This approach should be considered for biopsy of distal and posterior lesions. We strongly recommend the use of direct microscopic view to identify the medullary vessels, confirm the midline entry point, and avoid potential shift of the medulla. Further experience is needed to confirm safety and success rate of this approach.

Long-Term Outcome and Neuroimaging of Deep Brain Stimulation in Holmes Tremor: A Case Series.

BACKGROUND: Different deep brain stimulation (DBS) targets have been suggested as treatment for patients with pharmacologically refractory Holmes tremor (HT). We report the clinical and quality of life (QoL) long-term (up to nine years) outcome in four patients with HT treated with DBS (in thalamic ventral intermediate nucleus-VIM or in dentato-rubro-thalamic tract-DRTT). MATERIALS AND METHODS: The patients underwent routine clinical evaluations before and after DBS (typically annually). Tremor severity and activities of daily living (ADL) were quantified by the Fahn-Tolosa-Marin Tremor-Rating-Scale (FTMTRS). QoL was assessed using the RAND SF-36-item Health Survey (RAND SF-36). In addition, we computed, in all four patients, the VTA based on the best stimulation settings using heuristic approaches included in the open source toolbox LEAD-DBS. RESULTS: In all patients, tremor and ADL improved significantly at one-year post-DBS follow-up (34-61% improvement in FTMTRS total score compared to baseline). In three out of four patients, the improvement of tremor was sustained no longer than two to three years and only in one patient was sustained up to nine years. In this patient, the largest intersection between VTA and DBS target has been observed. Scores for ADL deteriorated over the course of time, reaching worse levels compared to baseline already during the three-year post-DBS follow-up, in three out of four patients. Physical and mental health component scores of RAND SF-36 had very different outcome between patients and follow-ups and were not associated with tremor-related outcomes. CONCLUSIONS: The benefits of DBS in HT might not be always long lasting. Although QoL slightly improved, this change seemed to be independent of the motor outcome following DBS. The estimation of DBS target and VTA proximity could be a useful tool for DBS clinicians in order to facilitate the DBS programming process and optimize DBS treatment.

Linear and nonlinear interrelations show fundamentally distinct network structure in preictal intracranial EEG of epilepsy patients.

Resection of the seizure generating tissue can be highly beneficial in patients with drug-resistant epilepsy. However, only about half of all patients undergoing surgery get permanently and completely seizure free. Investigating the dependences between intracranial EEG signals adds a multivariate perspective largely unavailable to visual EEG analysis, which is the current clinical practice. We examined linear and nonlinear interrelations between intracranial EEG signals regarding their spatial distribution and network characteristics. The analyzed signals were recorded immediately before clinical seizure onset in epilepsy patients who received a standardized electrode implantation targeting the mesiotemporal structures. The linear interrelation networks were predominantly locally connected and highly reproducible between patients. In contrast, the nonlinear networks had a clearly centralized structure, which was specific for the individual pathology. The nonlinear interrelations were overrepresented in the focal hemisphere and in patients with no or only rare seizures after surgery specifically in the resected tissue. Connections to the outside were predominantly nonlinear. In all patients without worthwhile improvement after resective treatment, tissue producing strong nonlinear interrelations was left untouched by surgery. Our findings indicate that linear and nonlinear interrelations play fundamentally different roles in preictal intracranial EEG. Moreover, they suggest nonlinear signal interrelations to be a marker of epileptogenic tissue and not a characteristic of the mesiotemporal structures. Our results corroborate the network-based nature of epilepsy and suggest the application of network analysis to support the planning of resective epilepsy surgery.

Pedunculopontine nucleus: An integrative view with implications on Deep Brain Stimulation.

The pedunculopontine nucleus (PPN) is a reticular nucleus located in the mesencephalic and upper pontine tegmentum. Initially, characterized by its predominant cholinergic projection neurons, it was associated with the "mesencephalic locomotor region" and "reticular activating system". Furthermore, based on histopathological studies, the PPN was hypothesized to play a role in the manifestation of symptoms in movement disorders such as Parkinson's disease (PD). Since axial symptoms represent unmet needs of PD treatments, a series of pioneering experiments in Parkinsonian monkeys promoted the idea of a potential new target for deep brain stimulation (DBS) and much clinical interest was generated in the following years leading to a number of trials analysing the role of PPN for gait disorders. This review summarizes the historical background and more recent findings about the anatomy and function of the PPN and its implications in the basal ganglia network of the normal as well as diseased brain. Classical views on PPN function shall be challenged by more recent findings. Additionally, the current role and future perspectives of PPN DBS in PD patients shall be outlined.

Directional local field potentials: A tool to optimize deep brain stimulation.

BACKGROUND: Although recently introduced directional DBS leads provide control of the stimulation field, programing is time-consuming. OBJECTIVES: Here, we validate local field potentials recorded from directional contacts as a predictor of the most efficient contacts for stimulation in patients with PD. METHODS: Intraoperative local field potentials were recorded from directional contacts in the STN of 12 patients and beta activity compared with the results of the clinical contact review performed after 4 to 7 months. RESULTS: Normalized beta activity was positively correlated with the contact's clinical efficacy. The two contacts with the highest beta activity included the most efficient stimulation contact in up to 92% and that with the widest therapeutic window in 74% of cases. CONCLUSION: Local field potentials predict the most efficient stimulation contacts and may provide a useful tool to expedite the selection of the optimal contact for directional DBS. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.