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Whether treatment response in patients with Parkinson disease depends on brain atrophy is insufficiently understood. The goal of this study is to identify specific atrophy patterns associated with response to dopaminergic therapy and deep brain stimulation.In this study, we analyzed the association of gray matter brain atrophy patterns, as identified by voxel-based morphometry, with acute response to levodopa (N = 118) and subthalamic nucleus deep brain stimulation (N = 39). Motor status was measured as a change in points on the Unified Parkinson's Disease Rating Scale III score. Baseline values were obtained before surgery, after cessation of dopaminergic medication for at least 12 hours; response to medication was assessed after administration of a standardized dose of levodopa. Response to deep brain stimulation was measured three months after surgery in the clinical condition after withdrawal of dopaminergic medication.Although frontoparietal brain gray matter loss was associated with subpar response to deep brain stimulation, there was no significant link between brain atrophy and response to levodopa.We conclude that response to deep brain stimulation relies on gray matter integrity; hence, gray matter loss may present a risk factor for poor response to deep brain stimulation and may be considered when making decision regarding clinical practice.

OBJECTIVE The treatment of symptomatic, progressive or recurrent acquired intracerebral cysts is challenging, especially when they are localized in eloquent structures. In addition to resection, endoscopic fenestration, or stereotactic puncture, the implantation of a cystoventricular shunt by stereotactic guidance (SCVS) has been reported as a minimally invasive procedure; however, only scarce data are available regarding its feasibility and efficacy. Here, the authors evaluated the feasibility and efficacy of frame-based SCVS in patients with acquired intracranial cysts. METHODS In this single-center retrospective analysis, the authors included all patients with acquired intracerebral cysts treated by SCVS following a standardized prospective protocol between 2012 and 2020. They analyzed clinical symptoms, complications, and radiological outcome with regard to cyst volume reduction by 3D volumetry. RESULTS Thirty-four patients (17 females and 17 males; median age 44 years, range 5–77 years) were identified. The median initial cyst volume was 11.5 cm3 (range 1.6–71.6 cm3), and the mean follow-up was 20 months (range 1–82 months). At the last follow-up, 27 of 34 patients (79%) showed a cyst volume reduction of more than 50%. Initial symptoms improved or resolved in 74% (n = 25) and remained stable in 24% (n = 8). No permanent clinical deterioration after treatment was observed. The total complication rate was 5.9%, comprising transient neurological deterioration (n = 1) and ventriculitis (n = 1). There were no deaths. The overall recurrence rate was 11.8%. CONCLUSIONS In this study, SCVS proved to be a safe, minimally invasive, and effective treatment with reliable long-term volume reduction, resulting in clinical improvement and a minor complication rate.

ObjectiveThis study aims to shed light on structural networks associated with stimulation-induced dysarthria (SID) and to derive a data-driven model to predict SID in patients with Parkinson’s Disease (PD) and deep brain stimulation (DBS) of the subthalamic nucleus (STN).MethodsRandomized, double-blinded monopolar reviews determining SID thresholds were conducted in 25 patients with PD and STN-DBS. A fiber-based mapping approach, based on the calculation of fiber-wise Odds Ratios for SID, was employed to identify the distributional pattern of SID in the STN’s vicinity. The ability of the data-driven model to classify stimulation volumes as “causing SID” or “not causing SID” was validated by calculating receiver operating characteristics (ROC) in an independent out-of-sample cohort comprising 14 patients with PD and STN-DBS.ResultsLocal fiber-based stimulation maps showed an involvement of fibers running lateral and postero-medial to the STN in the pathogenesis of SID, independent of the investigated hemisphere. ROC-analysis in the independent out-of-sample cohort resulted in a good fit of the data-driven model for both hemispheres (AUCleft= 0.88, AUCright= 0.88).InterpretationThis study reveals an involvement of both, cerebello-thalamic fibers, as well as the pyramidal tract, in the pathogenesis of SID in STN-DBS. The results may impact future postoperative programming strategies to avoid SID in patients with PD and STN-DBS.

OBJECTIVE To obtain individual clinical and neuroimaging data of patients undergoing Deep Brain Stimulation for essential tremor from five different European centers to identify predictors of outcome and to identify an optimal stimulation site. METHODS We analysed retrospectively baseline covariates, pre- and postoperative clinical tremor scores (12-month) as well as individual imaging data from 119 patients to obtain individual electrode positions and stimulation volumes. Individual imaging and clinical data was 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 greater than 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 cerebello-thalamic 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 greater than 50% tremor improvement with a sensitivity of 89% and a specificity of 57%. INTERPRETATION Our multicentre 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 deep brain stimulation in the future. This article is protected by copyright. All rights reserved.

Background: The satisfaction with life and, in particular, with treatment in Parkinson’s disease (PD) is understudied. Objective: To explore a new 7-item rating tool assessing satisfaction with life and treatment (SLTS-7) in PD. Methods: In this cross-sectional, multi-center study, including patients screened for advanced therapies, psychometric characteristics of the SLTS-7 were analyzed. An exploratory factor analysis identified the underlying factorial structure of the SLTS-7. Results: 117 patients were included, and the data quality of the SLTS-7 was excellent (computable data 100%), and acceptability measures satisfied standard criteria. Besides the global assessment (item 1), the exploratory factor analysis produced item 2 (physical satisfaction) as an independent item and two factors among the remaining items: items 3–5 (psycho-social satisfaction), and items 6 and 7 (treatment satisfaction). Cronbach’s alpha was 0.89, indicative of high internal consistency. The SLTS-7 total score correlated moderately with motor symptoms and weakly with non-motor symptoms total scores. SLTS-7 showed the highest correlations with the European Quality of Life with 5 items (EQ-5D) visual analog scale (0.43–0.58, p

IntroductionDeep brain stimulation (DBS) is an established treatment in patients with pharmaco-resistant neurological disorders of different ages. Surgical targeting and postoperative programming of DBS depend on the spatial location of the stimulating electrodes in relation to the surrounding anatomical structures and on electrode connectivity to a specific distributed pattern of brain networks. Such information is usually collected using group-level analysis which relies on the availability normative imaging-resources (atlases and connectomes). To this end, analyzing DBS data of children with debilitating neurological disorders like dystonia would make benefit from such resources, especially given the developmental differences between adults and children neuroimaging data. We assembled pediatric, normative neuroimaging-resources from open-access neuroimaging datasets and illustrated their utility on a cohort of children with dystonia treated with pallidal DBS. We aimed to derive a local pallidal sweetspot and explore a connectivity fingerprint associated with pallidal stimulation to exemplify the utility of the assembled imaging resources.MethodsA pediatric average brain template was implemented and used to localize DBS electrodes of twenty patients of the GEPESTIM registry cohort. Next, a pediatric subcortical atlas was also employed to highlight anatomical structures of interest. Local pallidal sweetspot was modeled and its degree of overlap with stimulation volumes was calculated as a correlate of individual clinical outcome. Additionally, a pediatric functional connectome of neurotypical subjects was built to allow network-based analyses and decipher a connectivity fingerprint responsible for clinical improvement in our cohort.ResultsWe successfully implemented a pediatric neuroimaging dataset that will be made available to public use as a tool for DBS-analyses. Overlap of stimulation volumes with the identified DBS-sweetspot model correlated significantly with improvement on a local spatial level (R = 0.46,permuted p= 0.019). Functional connectivity fingerprint of DBS-outcome was determined as a network correlate of therapeutic pallidal stimulation in children with dystonia (R = 0.30,permuted p= 0.003).ConclusionsLocal sweetspot and distributed network models provide neuroanatomical substrates for DBS-associated clinical outcome in dystonia using pediatric neuroimaging surrogate data. The current implementation of pediatric neuroimaging dataset might help improving the practice of DBS-neuroimaging analyses in pediatric patients.

Obsessive-compulsive disorder is among the most disabling psychiatric disorders. Although deep brain stimulation is considered an effective treatment, its use in clinical practice is not fully established. This is, at least in part, due to ambiguity about the best suited target and insufficient knowledge about underlying mechanisms. Recent advances suggest that changes in broader brain networks are responsible for improvement of obsessions and compulsions, rather than local impact at the stimulation site. These findings were fueled by innovative methodological approaches using brain connectivity analyses in combination with neuromodulatory interventions. Such a connectomic approach for neuromodulation constitutes an integrative account that aims to characterize optimal target networks. In this critical review, we integrate findings from connectomic studies and deep brain stimulation interventions to characterize a neural network presumably effective in reducing obsessions and compulsions. To this end, we scrutinize methodologies and seemingly conflicting findings with the aim to merge observations to identify common and diverse pathways for treating obsessive-compulsive disorder. Ultimately, we propose a unified network that-when modulated by means of cortical or subcortical interventions-alleviates obsessive-compulsive symptoms. https://doi.org/10.1016/j.biopsych.2021.07.010

Self-injurious behavior (SIB) is associated with diverse psychiatric conditions. Sometimes (e.g., in patients with autism spectrum disorder or acquired brain injuries), SIB is the most dominant symptom, severely restricting the psychosocial functioning and quality of life of the patients and inhibiting appropriate patient care. In severe cases, it can lead to permanent physical injuries or even death. Primary therapy consists of medical treatment and if implementable, behavioral therapy. For patients with severe SIB refractory to conventional therapy, neuromodulation can be considered as a last recourse. In scientific literature, several successful lesioning and deep brain stimulation targets have been described that can indicate a common underlying neuronal pathway. The objectives of this study were to evaluate the short- and long-term clinical outcome of patients with severe, therapy refractory SIB who underwent DBS with diverse underlying psychiatric disorders and to correlate these outcomes with the activated connectivity networks. We retrospectively analyzed 10 patients with SIB who underwent DBS surgery with diverse psychiatric conditions including autism spectrum disorder, organic personality disorder after hypoxic or traumatic brain injury or Tourette syndrome. DBS targets were chosen according to the underlying disorder, patients were either stimulated in the nucleus accumbens, amygdala, posterior hypothalamus, medial thalamus or ventrolateral thalamus. Clinical outcome was measured 6 months after surgery and at long-term follow-up after 10 or more years using the Early Rehabilitation Barthel index (ERBI) and time of restraint. Connectivity patterns were analyzed using normative connectome. Based on previous literature the orbitofrontal cortex, superior frontal gyrus, the anterior cingulate cortex, the amygdala and the hippocampus were chosen as regions of interest. This analysis showed a significant improvement in the functionality of the patients with DBS in the short- and long-term follow-up. Good clinical outcome correlated with higher connectivity to the amygdala and hippocampus. These findings may suggest a common pathway, which can be relevant when planning a surgical procedure in patients with SIB.

The occurrence of tics in Tourette syndrome (TS) has often been linked to impaired cognitive control, but empirical findings are still inconclusive. A recent view proposes that tics may be the result of an abnormally strong interrelation between perceptual processes and motor actions, commonly referred to as perception-action binding. The general aim of the present study was to examine proactive control and binding effects in the context of task switching in adult human patients with TS and matched healthy controls. A cued task switching paradigm was employed in 24 patients (18 male, 6 female) and 25 controls while recording electroencephalography (EEG). Residue iteration decomposition (RIDE) was applied to analyze cue-locked proactive cognitive control and target-locked binding processes. Behavioral task switching performance was unaltered in patients with TS. A cue-locked parietal switch positivity, reflecting proactive control processes involved in the reconfiguration of the new task did not differ between groups. Importantly, target-locked fronto-central (N2) and parietal (P3) modulations, reflecting binding processes between perception and action, differed between groups. Underlying neurophysiological processes were best depicted after temporal decomposition of the EEG signal. The present results argue for unaltered proactive control but altered perception-action binding processes in the context of task switching, supporting the view that the integration of perception and action is processed differently in patients TS. Future studies should further investigate the specific conditions under which binding may be altered in TS and the influence of top-down processes, such as proactive control, on bindings.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is a well-established treatment for patients with Parkinson’s disease. Previous acute challenge studies suggested that short pulse widths might increase the therapeutic window while maintaining motor symptom control with a decrease in energy consumption. However, only little is known about the effect of short pulse width stimulation beyond the setting of an acute challenge. Objective: To compare 4 weeks of STN-DBS with conventional pulse width stimulation (60 μs) to 4 weeks of STN-DBS with short pulse width stimulation (30 μs) regarding motor symptom control. Methods: This study was a monocentric, double-blinded, randomized crossover non-inferiority trial investigating whether short pulse width stimulation with 30 μs maintains equal motor control as conventional 60 μs stimulation over a period of 4 weeks (German Clinical Trials Register No. DRKS00017528). Primary outcome was the difference in motor symptom control as assessed by a motor diary. Secondary outcomes included energy consumption measures, non-motor effects, side-effects, and quality of life. Results: Due to a high dropout rate, the calculated sample size of 27 patients was not met and 24 patients with Parkinson’s disease and STN-DBS were included in the final analysis. However, there were no differences in any investigated outcome parameter between the two treatment conditions. Conclusion: This study demonstrates that short pulse width settings (30 μs) provide non-inferior motor symptom control as conventional (60 μs) stimulation without significant differences in energy consumption. Future studies are warranted to evaluate a potential benefit of short pulse width settings in patients with pronounced dyskinesia.

OBJECTIVE 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). METHODS 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. RESULTS 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

Background: Directional leads are increasingly used in deep brain stimulation. They allow shaping the electrical field in the axial plane. These new possibilities increase the complexity of programming. Thus, optimized programming approaches are needed to assist clinical testing and to obtain full clinical benefit. Objectives: This simulation study investigates to what extent the electrical field can be shaped by directional steering to compensate for lead malposition. Method: Binary volumes of tissue activated (VTA) were simulated, by using a finite element method approach, for different amplitude distributions on the three directional electrodes. VTAs were shifted from 0 to 2 mm at different shift angles with respect to the lead orientation, to determine the best compensation of a target volume. Results: Malpositions of 1 mm can be compensated with the highest gain of overlap with directional leads. For larger shifts, an improvement of overlap of 10–30% is possible, depending on the stimulation amplitude and shift angle of the lead. Lead orientation and shift determine the amplitude distribution of the electrodes. Conclusion: To get full benefit from directional leads, both the shift angle as well as the shift to target volume are required to choose the correct amplitude distribution on the electrodes. Current directional leads have limitations when compensating malpositions >1 mm; however, they still outperform conventional leads in reducing overstimulation. Further, their main advantage probably lies in the reduction of side effects. Databases like the one from this simulation could serve for optimized lead programming algorithms in the future.

Background: Directional deep brain stimulation (DBS) enlarges the therapeutic window by increasing side-effect thresholds and improving clinical benefits. To determine the optimal stimulation settings and interpret clinical observations, knowledge of the lead orientation in relation to the patient’s anatomy is required. Objective: To determine if directional leads remain in a fixed orientation after implantation or whether orientation changes over time. Method: Clinical records of 187 patients with directional DBS electrodes were screened for CT scans in addition to the routine postoperative CT. The orientation angle of each electrode at a specific point in time was reconstructed from CT artifacts using the DiODe algorithm implemented in Lead-DBS. The orientation angles over time were compared with the originally measured orientations from the routine postoperative CT. Results: Multiple CT scans were identified in 18 patients and the constancy of the orientation angle was determined for 29 leads at 48 points in time. The median time difference between the observations and the routine postoperative CT scan was 82 (range 1–811) days. The mean difference of the orientation angles compared to the initial measurement was –1.1 ± 3.9° (range –7.6 to 8.7°). Linear regression showed no relevant drift of the absolute value of the orientation angle over time (0.8°/year, adjusted R2: 0.040, p = 0.093). Conclusion: The orientation of directional leads was stable and showed no clinically relevant changes either in the first weeks after implantation or over longer periods of time.

Recent translational data suggest that deep brain stimulation (DBS) of the cortico-striato-thalamo-cortical (CSTC) loops improves sensorimotor gating in psychiatric disorders that show deficient prepulse inhibition (PPI), a robust operational measure of sensorimotor gating. To our knowledge we are the first to investigate this effect in patients with Tourette syndrome (TS). We measured PPI of the acoustic startle reflex in patients with TS (N = 10) or Obsessive-Compulsive Disorder (OCD) (N = 8) treated with DBS of the centromedian and ventro-oral internal thalamic nucleus and the anterior limb of internal capsule-nucleus accumbens area respectively, and aged- and gender-matched healthy controls (HC). PPI of the DBS groups was measured in randomized order in the ON and OFF stimulation condition. Statistical analysis revealed no significant difference in PPI (%) of patients with TS between ON (M = 20.5, SD = 14.9) and OFF (M = 25.2, SD = 29.7) condition. There were significantly reduced PPI levels in patients with TS in the ON condition compared to HC (M = 49.2, SD = 10.7), but no significant difference in PPI between TS in the OFF condition and HC. Furthermore, we found no significant stimulation or group effect for OCD and HC (OCD ON: M = 57.0, SD = 8.3; OCD OFF: 67.8, SD = 19.6; HC: M = 63.0, SD = 24.3). Our study has a number of limitations. Sample sizes are small due to the restricted patient collective. The study was not controlled for use of psychoactive medication or nicotine. Furthermore, we were not able to assess presurgical PPI measurements. In conclusion, we were able to show that PPI is impaired in patients with TS. This finding is in line with recent translational work. With respect to the OCD cohort we were not able to replicate our previously published data. A disability in sensorimotor gating plays a pivotal role in many psychiatric disorders therefore more research should be conducted to disentangle the potential and limitations of modulating sensorimotor gating via brain stimulation techniques.

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

The pterygopalatine fossa (PPF) is a complex and paired anatomical structure located at the skull base. A clinically and surgically relevant structure located in the pterygopalatine fossa is the sphenopalatine ganglion. Electrical stimulation of the sphenopalatine ganglion is one possible method of treating cluster headache. The pterygomaxillary fissure (PMF) defines the pterygopalatine fossa laterally and determines the surgical approach. As part of preoperative surgical planning, each patient undergoes a preoperative head computed tomography or a cone beam computed tomography. In our study cone beam computed tomography images of 90 male and 110 female PMF were analyzed. Generally, males have a wider fissure than females. Moreover, a significant inter-subject difference could be shown between males and females. The analysis of the right and left PMF according to gender and age does not show any significant intra-subject differences. Following an established protocol for high-resolution CT images the measurements were classified into four fissure types and also analyzed according to gender and age. Fissure type I is significantly more often present in males, whereas the smaller fissure types (II, III, and IV) are significantly more often found in females. Older patients presented statistically significant more often with type I, whereas the younger patients showed more often the narrower types II and IV. Due to the fact that narrow fissures smaller than 2 mm could limit the insertion of neurostimulator implants in the PPF, special attention should be paid to females and younger patients during preoperative planning.

Contains fulltext : 241592.pdf (Publisher’s version ) (Open Access) Objectives: Obsessive-compulsive disorder (OCD) is a psychiatric disorder with alterations of cortico-striato-thalamo-cortical loops and impaired performance monitoring. Electrophysiological markers such as conflict-related medial frontal theta (MFT) and error-related negativity (ERN) may be altered by clinically effective deep brain stimulation (DBS) of the anterior limb of the internal capsule and nucleus accumbens (ALIC/NAc). We hypothesized that ALIC/NAc DBS modulates electrophysiological performance monitoring markers. Materials and Methods: Fifteen patients (six male) with otherwise treatment-refractory OCD receiving ALIC/NAc DBS performed a flanker task with EEG recordings at three sessions: presurgery, and at follow-up with DBS on and off. We examined MFT, ERN, and task performance. Furthermore, we investigated interrelations with clinical efficacy and the explored the influence of the location of individual stimulation volumes on EEG modulations. Results: MFT and ERN were significantly attenuated by DBS with differences most pronounced between presurgery and DBS-on states. Also, we observed reaction time slowing for erroneous responses during DBS-off. Larger presurgery ERN amplitudes were associated with decreased clinical efficacy. Exploratory anatomical analyses suggested that stimulation volumes encompassing the NAc were associated with MFT modulation, whereas ALIC stimulation was associated with modulation of the ERN and clinical efficacy. Conclusion: ALIC/NAc DBS diminished MFT and ERN, demonstrating modulation of the medial frontal performance monitoring system in OCD. Furthermore, our findings encourage further studies to explore the ERN as a potential predictor for clinical efficacy. 8 p.

Background: Hyperkinetic movement disorders secondary to brain tissue damage due to hyperglycemia are a rare complication of diabetes mellitus. Nonketotic hyperglycemic hemichorea (NH-HC) is characterized by a rapid onset of involuntary movements after increased serum glucose levels. Case Description: We report on a case of a 62-year-old male patient with a 28-year history of Type II diabetes mellitus with NH-HC following an infect-associated exacerbation of blood glucose levels. Choreiform movements of the right upper extremity, face, and trunk persisted 6 months after onset. Due to failure of conservative treatments, we opted for unilateral deep brain stimulation of the globus pallidus internus, which led to complete cessation of symptoms within a week after initial programming. Symptom control was still satisfactory 12 months after surgery. No side-effects or surgery-associated complications were observed. Conclusion: Globus pallidus internus DBS is an effective and safe treatment option for hyperkinetic movement disorders secondary to brain tissue damage caused by hyperglycemia. Postoperatively, stimulation effects can be observed quickly and effects persist even after 12 months.

Directional deep brain stimulation (DBS) leads are now widely used, but the orientation of directional leads needs to be taken into account when relating DBS to neuroanatomy. Methods that can reliably and unambiguously determine the orientation of directional DBS leads are needed. In this study, we provide an enhanced algorithm that determines the orientation of directional DBS leads from postoperative CT scans. To resolve the ambiguity of symmetric CT artifacts, which in the past, limited the orientation detection to two possible solutions, we retrospectively evaluated four different methods in 150 Cartesia™ directional leads, for which the true solution was known from additional X-ray images. The method based on shifts of the center of mass (COM) of the directional marker compared to its expected geometric center correctly resolved the ambiguity in 100% of cases. In conclusion, the DiODe v2 algorithm provides an open-source, fully automated solution for determining the orientation of directional DBS leads.

BackgroundDeep brain stimulation (DBS) of the medial thalamus is an evolving therapy for severe, treatment-refractory Tourette syndrome (TS). It remains unanswered which functionally connected networks need to be modulated to obtain optimal treatment results.MethodsWe assessed treatment response of 15 patients with TS untergoing thalamic DBS six and twelve months postoperatively using the Yale Global Tic Severity Scale (YGTSS) tic score. For each time point, functional connectivity maps seeding from stimulation sites were calculated based on a normative functional connectome derived from 1000 healthy subjects. Resulting maps were analyzed in a voxel-wise mixed model for repeated measurements to identify patterns of connectivity associated with tic reduction.ResultsConnectivity of stimulation to the medial frontal cortex, bilateral insulae and sensorimotor cortex was associated with tic reduction. Connectivity with the temporal lobe, cerebellum, ventral striatum and orbitofrontal cortex was negatively associated. The overall connectivity pattern was robust to leave-one-out cross-validation, explaining 25 % of outcome variance (R = 0.500; p = 0.005).ConclusionsWe delineated a functional connectivity profile seeding from stimulation sites associated with TS-DBS outcome. This pattern comprised areas linked to the processing of premonitory urges and tic execution, thereby extending our current understanding of effective neuromodulation for TS.

The development of robotic systems has provided an alternative to frame-based stereotactic procedures. The aim of this experimental phantom study was to compare the mechanical accuracy of the Robotic Surgery Assistant (ROSA) and the Leksell stereotactic frame by reducing clinical and procedural factors to a minimum.To precisely compare mechanical accuracy, a stereotactic system was chosen as reference for both methods. A thin layer CT scan with an acrylic phantom fixed to the frame and a localizer enabling the software to recognize the coordinate system was performed. For each of the five phantom targets, two different trajectories were planned, resulting in 10 trajectories. A series of five repetitions was performed, each time based on a new CT scan. Hence, 50 trajectories were analyzed for each method. X-rays of the final cannula position were fused with the planning data. The coordinates of the target point and the endpoint of the robot- or frame-guided probe were visually determined using the robotic software. The target point error (TPE) was calculated applying the Euclidian distance. The depth deviation along the trajectory and the lateral deviation were separately calculated.Robotics was significantly more accurate, with an arithmetic TPE mean of 0.53 mm (95% CI 0.41-0.55 mm) compared to 0.72 mm (95% CI 0.63-0.8 mm) in stereotaxy (Both the robotic and frame-based approach proved accurate. The robotic procedure showed significantly higher accuracy. For both methods, procedural factors occurring during surgery might have a more relevant impact on overall accuracy.

Contains fulltext : 214745.pdf (Publisher’s version ) (Closed access) 3 p.

OBJECTIVE To investigate whether functional sweet spots of deep brain stimulation (DBS) in the subthalamic nucleus (STN) can predict motor improvement in Parkinson disease (PD) patients. METHODS Stimulation effects of 449 DBS settings in 21 PD patients were clinically and quantitatively assessed through standardized monopolar reviews and mapped into standard space. A sweet spot for best motor outcome was determined using voxelwise and nonparametric permutation statistics. Two independent cohorts were used to investigate whether stimulation overlap with the sweet spot could predict acute motor outcome (10 patients, 163 settings) and long-term overall Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) improvement (63 patients). RESULTS Significant clusters for suppression of rigidity and akinesia, as well as for overall motor improvement, resided around the dorsolateral border of the STN. Overlap of the volume of tissue activated with the sweet spot for overall motor improvement explained R2 = 37% of the variance in acute motor improvement, more than triple what was explained by overlap with the STN (R2 = 9%) and its sensorimotor subpart (R2 = 10%). In the second independent cohort, sweet spot overlap explained R2 = 20% of the variance in long-term UPDRS-III improvement, which was equivalent to the variance explained by overlap with the STN (R2 = 21%) and sensorimotor STN (R2 = 19%). INTERPRETATION This study is the first to predict clinical improvement of parkinsonian motor symptoms across cohorts based on local DBS effects only. The new approach revealed a distinct sweet spot for STN DBS in PD. Stimulation overlap with the sweet spot can predict short- and long-term motor outcome and may be used to guide DBS programming. ANN NEUROL 2019;86:527-538.

To predict radiation-induced lung injury and outcome in non-small cell lung cancer (NSCLC) patients treated with robotic stereotactic body radiation therapy (SBRT) from radiomic features of the primary tumor. In all, 110 patients with primary stage I/IIa NSCLC were analyzed for local control (LC), disease-free survival (DFS), overall survival (OS) and development of local lung injury up to fibrosis (LF). First-order (histogram), second-order (GLCM, Gray Level Co-occurrence Matrix) and shape-related radiomic features were determined from the unprocessed or filtered planning CT images of the gross tumor volume (GTV), subjected to LASSO (Least Absolute Shrinkage and Selection Operator) regularization and used to construct continuous and dichotomous risk scores for each endpoint. Continuous scores comprising 1–5 histogram or GLCM features had a significant (p = 0.0001–0.032) impact on all endpoints that was preserved in a multifactorial Cox regression analysis comprising additional clinical and dosimetric factors. At 36 months, LC did not differ between the dichotomous risk groups (93% vs. 85%, HR 0.892, 95%CI 0.222–3.590), while DFS (45% vs. 17%, p

BackgroundFor more than 15 years, deep brain stimulation (DBS) has served as a last-resort treatment for severe treatment-resistant obsessive-compulsive disorder (OCD).MethodsFrom 2010 to 2016, 20 patients with OCD (10 men/10 women) were included in a single-centre trial with a naturalistic open-label design over 1 year to evaluate the effects of DBS in the anterior limb of the internal capsule and nucleus accumbens region (ALIC-NAcc) on OCD symptoms, executive functions, and personality traits.ResultsALIC-NAcc-DBS significantly decreased OCD symptoms (mean Yale-Brown Obsessive Compulsive Scale reduction 33%, 40% full responders) and improves global functioning without loss of efficacy over 1 year. No significant changes were found in depressive or anxiety symptoms. Our study did not show any effect of ALIC-NAcc-DBS on personality traits or executive functions, and no potential outcome predictors were identified in a post hoc analysis. Other than several individual minor adverse events, ALIC-NAcc-DBS has been shown to be safe, but 35% of patients reported a sudden increase in anxiety and anhedonia after acute cessation of stimulation.ConclusionsWe conclude that ALIC-NAcc-DBS is a well-tolerated and promising last-resort treatment option for OCD. The cause of variability in the outcome remains unclear, and the aspect of reversibility must be examined critically. The present data from one of the largest samples of patients with OCD treated with DBS thus far support the results of previous studies with smaller samples.

Background Multiple deep brain stimulation (DBS) targets have been proposed for treating intractable obsessive-compulsive disorder (OCD). Here, we investigated whether stimulation effects of different target sites would be mediated by one common or several segregated functional brain networks. Methods First, seeding from active electrodes of 4 OCD patient cohorts (N = 50) receiving DBS to anterior limb of the internal capsule or subthalamic nucleus zones, optimal functional connectivity profiles for maximal Yale-Brown Obsessive Compulsive Scale improvements were calculated and cross-validated in leave-one-cohort-out and leave-one-patient-out designs. Second, we derived optimal target-specific connectivity patterns to determine brain regions mutually predictive of clinical outcome for both targets and others predictive for either target alone. Functional connectivity was defined using resting-state functional magnetic resonance imaging data acquired in 1000 healthy participants. Results While optimal functional connectivity profiles showed both commonalities and differences between target sites, robust cross-predictions of clinical improvements across OCD cohorts and targets suggested a shared network. Connectivity to the anterior cingulate cortex, insula, and precuneus, among other regions, was predictive regardless of stimulation target. Regions with maximal connectivity to these commonly predictive areas included the insula, superior frontal gyrus, anterior cingulate cortex, and anterior thalamus, as well as the original stereotactic targets. Conclusions Pinpointing the network modulated by DBS for OCD from different target sites identified a set of brain regions to which DBS electrodes associated with optimal outcomes were functionally connected—regardless of target choice. On these grounds, we establish potential brain areas that could prospectively inform additional or alternative neuromodulation targets for obsessive-compulsive disorder.

BackgroundThe effects of subthalamic stimulation (subthalamic nucleus-deep brain stimulation, STN-DBS) on impulsive and compulsive behaviours (ICB) in Parkinson’s disease (PD) are understudied.ObjectiveTo investigate clinical predictors of STN-DBS effects on ICB.MethodsIn this prospective, open-label, multicentre study in patients with PD undergoing bilateral STN-DBS, we assessed patients preoperatively and at 6-month follow-up postoperatively. Clinical scales included the Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS), PD Questionnaire-8, Non-Motor Symptom Scale (NMSS), Unified PD Rating Scale in addition to levodopa-equivalent daily dose total (LEDD-total) and dopamine agonists (LEDD-DA). Changes at follow-up were analysed with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We explored predictors of QUIP-RS changes using correlations and linear regressions. Finally, we dichotomised patients into ‘QUIP-RS improvement or worsening’ and analysed between-group differences.ResultsWe included 55 patients aged 61.7 years±8.4 with 9.8 years±4.6 PD duration. QUIP-RS cut-offs and psychiatric assessments identified patients with preoperative ICB. In patients with ICB, QUIP-RS improved significantly. However, we observed considerable interindividual variability of clinically relevant QUIP-RS outcomes as 27.3% experienced worsening and 29.1% an improvement. In post hoc analyses, higher baseline QUIP-RS and lower baseline LEDD-DA were associated with greater QUIP-RS improvements. Additionally, the ‘QUIP-RS worsening’ group had more severe baseline impairment in the NMSS attention/memory domain.ConclusionsOur results show favourable ICB outcomes in patients with higher preoperative ICB severity and lower preoperative DA doses, and worse outcomes in patients with more severe baseline attention/memory deficits. These findings emphasise the need for comprehensive non-motor and motor symptoms assessments in patients undergoing STN-DBS.Trial registration numberDRKS00006735.

Die funktionelle Neurochirurgie umfasst die Operationen am zentralen und peripheren Nervensystem, um eine elektrische Dysfunktion, die zu bestimmten neurologischen Symptomen fuhrt, zu modifizieren und dadurch diese Symptome zu lindern. Zu den operativen Eingriffen der funktionellen Neurochirurgie gehoren zum einen die tiefe Hirnstimulation (THS), wobei hier der Morbus Parkinson eine der bekanntesten und haufigsten Indikationen darstellt, zum anderen die operative Behandlung chronischer Schmerzen und neuerdings auch der Demenzerkrankung. In diesem Kapitel werden sowohl die Moglichkeiten und Besonderheiten der operativen Therapie der chronischen Schmerzen als auch die Behandlungsoptionen im Rahmen der tiefen Hirnstimulation bei Patienten in hoherem Lebensalter dargelegt.

When choosing between rewards that differ in temporal proximity (inter-temporal choice), human preferences are typically stable, constituting a clinically-relevant transdiagnostic trait. Here we show in patients undergoing deep brain stimulation (DBS) of the anterior limb of the internal capsule / nucleus accumbens region for treatment-resistant obsessivecompulsive disorder (OCD), that long-term chronic (but not phasic) DBS disrupts inter-temporal preferences. Hierarchical Bayesian modeling accounting for temporal discounting behavior across multiple time points allowed us to assess both short-term and long-term reliability of inter-temporal choice. In controls, temporal discounting was highly reliable, both long-term (6 months) and short-term (1 week). In contrast, in patients undergoing DBS, short-term reliability was high, but long-term reliability (6 months) was severely disrupted. Control analyses confirmed that this effect was not due to range restriction, the presence of OCD symptoms or group differences in choice stochasticity. Model-agnostic between- and within-subject analyses confirmed this effect. These findings provide initial evidence for long-term modulation of cognitive function via DBS and highlight a potential contribution of the human nucleus accumbens region to inter-temporal preference stability over time.Significance StatementChoosing between rewards that differ in temporal proximity is in part a stable trait with relevance for many mental disorders, and depends on prefrontal regions and regions of the dopamine system. Here we show that chronic deep brain stimulation (DBS) of the human anterior limb of the internal capsule / nucleus accumbens region for treatment-resistant obsessive compulsive disorder disrupts the stability of inter-temporal preferences. These findings show that chronic stimulation of one of the brain’s central motivational hubs can disrupt preferences thought to depend on this circuit.

For successful goal-directed behavior, a performance monitoring system is essential. It detects behavioral errors and initiates behavioral adaptations to improve performance. Two electrophysiological potentials are known to follow errors in reaction time tasks: the error-related negativity (ERN), which is linked to error processing, and the error positivity (Pe), which is associated with subjective error awareness. Furthermore, the correct-related negativity (CRN) is linked to uncertainty about the response outcome. Here we attempted to identify the involvement of the nucleus accumbens (NAc) in the aforementioned performance monitoring processes. To this end, we simultaneously recorded cortical activity (EEG) and local field potentials (LFP) during a flanker task performed by four patients with severe opioid abuse disorder who underwent electrode implantation in the NAc for deep brain stimulation. We observed significant accuracy-related modulations in the LFPs at the time of the ERN/CRN in two patients and at the time of Pe in three patients. These modulations correlated with the ERN in 2/8, with CRN in 5/8 and with Pe in 6/8, recorded channels, respectively. Our results demonstrate the functional interrelation of striatal and cortical processes in performance monitoring specifically related to error processing and subjective error awareness.

Postoperative choice of the most effective DBS contact in patients with essential tremor (ET) so far relies on lengthy clinical testing. It has been shown 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 the stimulation overlap with the individual DRTT. Seven ET patients with bilateral thalamic deep brain stimulation were included retrospectively. Tremor control was assessed contact-wise during test stimulation with 2mA. The individual DRTTs were identified from diffusion tensor imaging. Contacts were ranked by their overlap of the test stimulation 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 92.9 % of the cases, the contact with the best clinical effect was the contact with the highest or second-highest DRTT-overlap. On the group level, the DRTT-overlap explained 26.7% of the variance of the clinical outcome (p

Objectives: To generate and validate a state-of-the-art radiomics model for prediction of radiation-induced lung injury and oncologic outcome in non-small cell lung cancer (NSCLC) patients treated with robotic stereotactic body radiation therapy (SBRT).Methods: A radiomics model was generated from the planning CT images of 110 patients with primary, inoperable stage I/IIa NSCLC who were treated with robotic SBRT using a risk-adapted fractionation scheme at the University Hospital Cologne (training cohort). In total, 851 radiomic features fulfilling the standards of the Image Biomarker Standardization Initiative (IBSI) were extracted from the outlined gross tumor volume (GTV) and used to build a model for prediction of local control (LC), disease-free survival (DFS), overall survival (OS) and development of local lung fibrosis (LF) by means of a gradient-boosted ensemble of regression trees. In addition, predictive clinical and dosimetric parameters were identified from a standard univariate Cox regression analysis. The radiomics model was validated in a comparable cohort of 71 patients treated by robotic SBRT at the Radiosurgery Center in Northern Germany (test cohort).Results: Oncologic outcome did not differ between the two cohorts (OS at 36 months 56% vs. 43%, p=0.065; median DFS 25 months vs. 23 months, p=0.43; LC at 36 months 90% vs. 93%, p=0.197). Local lung fibrosis developed in 33% vs. 35% of the patients (p=0.75), all events were observed within 36 months. In the training cohort, the radiomics model was able to distinguish low-risk from high risk patients for OS, DFS, LC and LF with a high accuracy (p < 0.001). In the test cohort, the model for development of lung fibrosis retained its predictive power and could differentiate patients with a high risk for developing LF from those with a low risk (p=0.016). In contrast, the radiomics model failed to predict OS, DFS and LC in the test cohort. Also, none of the clinical and dosimetric parameters predictive for development of LF in the training cohort (GTV-Dmean, GTV-Dmax, PTV-D95%, Lung-D1ml, age) had a significant impact on the occurrence of LF in the test cohort.Conclusion: Despite the obvious difficulties in generalizing predictive models for oncologic outcome and toxicity, this analysis shows that a carefully designed radiomics model for prediction of local lung fibrosis after SBRT of early stage lung cancer performs well across different institutions.

ObjectiveOpen questions remain regarding the optimal target, or sweetspot, for deep brain stimulation (DBS) in e.g. Parkinson’s Disease. Previous studies introduced different methods of mapping DBS effects to determine sweetspots. While having a direct impact on surgical targeting and postoperative programming in DBS, these methods so far have not been investigated in ground-truth data.Materials & MethodsThis study investigated five previously published DBS mapping methods regarding their potential to correctly identify a ground-truth sweetspot. Methods were investigated in silico in eight different use-case scenarios, which incorporated different types of clinical data, noise, and differences in underlying neuroanatomy. Dice-coefficients were calculated to determine the overlap between identified sweetspots and the ground-truth. Additionally, out-of-sample predictive capabilities were assessed using the amount of explained variance R2.ResultsThe five investigated methods resulted in highly variable sweetspots. Methods based on voxel-wise statistics against average outcomes showed the best performance overall. While predictive capabilities were high, even in the best of cases Dice-coefficients remained limited to values around 0.5, highlighting the overall limitations of sweetspot identification.ConclusionsThis study highlights the strengths and limitations of current approaches to DBS sweetspot mapping. Those limitations need to be taken into account when considering the clinical implications. All future approaches should be investigated in silico before being applied to clinical data.

OBJECTIVES: We aimed to investigate the efficacy of new subperception stimulation paradigms including 1.2 kHz-high-frequency stimulation (HFS) and advanced-HFS field-shaping algorithm (dorsal horn HFS [DHHFS]) in refractory cases which initially benefited from conventional spinal cord stimulation (SCS) and lost the effect throughout time. MATERIALS AND METHODS: In the context of a rescue-therapy, patients underwent externalization of the implanted SCS-leads and were tested with multiple combinations of new SCS paradigms. Pain intensity was analyzed using the numeric rating scale (NRS), and data were collected preoperatively and at multiple postoperative follow-ups. RESULTS: Thirty-seven patients underwent externalization of the leads. Mean preoperative NRS-score was 8.1/10 points (SD ± 0.9) for the ON-stimulation period. Patients received a combination of either tonic, burst and 1.2 kHz-HFS, or burst and 1.2 kHz-HFS, DHHFS, or 1.2 kHz-HFS and DHHFS, or 1.2 kHz-HFS alone. The mean postoperative NRS-score after the testing-phase was 3.8/10 points (SD ± 2.5), showing a 48.0% mean reduction (p < 0.001). In total, 29 patients reported a significant reduction above 50% in NRS-scores and therefore were reimplanted with new generators that could deliver the new paradigms. Eight patients underwent full SCS-system explantation. The patients who continued with the new paradigms (n = 29) reported mean NRS-scores of 3.5/10 points (SD ± 1.7) 12 months postoperatively, still showing a significant reduction of 43.3% when compared to preoperative scores (p < 0.001). CONCLUSION: Rescue-therapy with combination of multiple waveforms, including tonic, burst, 1.2 kHz-HFS, and DHHFS, was associated with a significant pain relief in patients with failed conventional SCS. This approach is a safe and efficient and should be considered before explantation of the SCS-system.

The aim of this study was to provide volumetric data of the pterygopalatine fossa by semiautomatic segmentation based upon cone beam computed tomography.Cone beam computed tomography (CBCT) images of 100 patients were analyzed. By using the open source software "ITK-Snap," the volumetric measurements of 200 pterygopalatine fossae were performed. For statistical investigations paired t test, and independent Student t test were performed. Also, the Pearsons chi-square test was applied. P values P 0.05 were considered significant.The mean volume was 578.376 mm for the right and 560.979 mm for the left side. The results indicated statistically significant differences according to the right and the left pterygopalatine fossa, regardless of gender (P 0.05). The analysis of differences between males and females did not show any significant results (P 0.05), although males present a slightly larger volume than females. According to the median age (59 years), younger patients presented smaller volumes, whereas older patients presented larger volumes. Nevertheless, no statistically significant differences according to age (χ = 3.520; P 0.05) could be found.Clinical intervention with the application of local anesthetics into the complex and vulnerable anatomy of the pterygopalatine fossa makes a thorough knowledge about the volumetric capacity indispensable. Therefore, the semiautomatic segmentation of CBCT images provides a useful, available and validated tool. Our results show that a final injected anesthetic volume larger than 1 ml exceeds the pterygopalatine fossa capacity considerably and could cause complications. To prevent this, volumetric analysis of this region can provide further information and enables an individualized patients' treatment.

Thalamic deep brain stimulation (DBS) is an effective treatment for patients with medically refractory essential tremor. However, stimulation-induced side-effects, especially stimulation-induced dysarthria (SID), interfere severely with quality of life and postoperative tremor control. Here, we present a functional and structural network approach to SID to gain insights into the associated brain areas and to predict stimulation-induced worsening of intelligibility. Monopolar reviews were conducted in 14 essential tremor patients with bilateral thalamic DBS by increasing the stimulation amplitude contact-wise until (i) a maximum of 10mA, (ii) the occurrence of intolerable side effects, or (iii) the onset of SID. Speech assessments included intelligibility ratings when reading a German standard text and a fast syllable repetition task. To detect brain areas associated with SID, a functional connectivity difference image of volumes of tissue activated (VTAs) causing SID, and VTAs not causing SID was created employing a state-of-the-art functional connectome, Lead-DBS, as well as the SPM toolbox. Additionally, discriminative fibers for stimulation-induced worsening of intelligibility were identified in a structural connectome using linear mixed effect models and validated in a leave-one-out design. A total of 111 contact assessments were included for further analysis. The functional connectivity difference image indicated stronger connectivity of VTAs causing SID (N = 51) to the precentral gyrus with a positive medio-lateral gradient, parts of the inferior and medial frontal gyrus, the supramarginal gyrus, the superior temporal gyrus, as well as the superior and the inferior cerebellar lobules, and the vermis. In the thalamic region, discriminative fibers for stimulation-induced worsening of intelligibility were located antero-laterally to fibers associated with tremor control as published by Al-Fatly et al. (2019). The overlap of the respective clinical stimulation setting’s VTAs with these fibers explained 33.2% of the variance of individual change in intelligibility compared to “OFF stimulation” in a leave-one-out design. This study demonstrates that SID in essential tremor patients is related to a modulation of the functional connectome of speech production by thalamic DBS. In spite of the proximity of functional and structural connectivity patterns for tremor control, as identified by Al-Fatly et al. (2019), and deterioration of speech, as identified in the present study, we were able to derive a fiber-based atlas structure, that could help to avoid SID in essential tremor patients. These findings might contribute to future lead placement and postoperative programming strategies.

Deep brain stimulation (DBS) is a neurosurgical treatment with a growing range of indications. The number of clinical studies is expanding because of DBS for new indications and efforts to improve DBS for existing indications. To date, various methods have been used to perform DBS studies. Designing a clinical intervention study with active implantable medical devices has specific challenges while expanding patient treatment. This paper provides an overview of the key aspects that are essential for setting up a DBS study.

BACKGROUND: The pathophysiology of pain in patients with symptomatic thoracic disc herniation (TDH) remains poorly understood. Mere mechanical compression of the spinal cord and/or the exiting nerve root by a prolapsed disc cannot explain the pathogenesis of pain in all cases. Previous studies report a direct correlation between the levels of proinflammatory cytokines in disc biopsies and the severity of leg pain in patients with lumbar disc herniation. A similar correlation in patients with TDH has not been investigated.PURPOSE: To correlate the cerebrospinal fluid (CSF) expression of cytokines and pain-related amino acids with preoperative pain scores in patients with symptomatic TDH.STUDY DESIGN: A prospective human study of CSF samples and clinical outcome scores.METHODS: Using enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC), we determined inflammatory cytokine levels (TNF-alpha, IL-1 beta, and IL-10) and amino acid levels (glutamate, aspartate, gamma-aminobutyric acid, glycine, and arginine) in CSF samples from 10 patients with TDH and 10 control subjects who did not suffer an inflammatory disease nor pain related to spinal cord compression and subsequently correlated these levels with preoperative pain scores. Differences between both groups were evaluated by a Mann-Whitney U test. In order to estimate the correlation between cytokine or amino acid expression and pain scores, data were analyzed using a linear regression analysis.RESULTS: No inflammatory cytokines were found in CSF samples from control subjects, whereas TNF-a, IL-1b, and IL-10 were detectable by ELISA in all CSF samples from patients with TDH. TNF-a and IL-10 but not IL-1b levels moderately correlated with preoperative pain scores. Elevated TNF-alevels positively correlated with high pain scores; elevated IL-10 levels negatively correlated with high pain scores. Amino acids were detectable in all samples from both groups. There were no significant differences between the groups in any of the amino acids measured with HPLC.CONCLUSION: Increased proinflammatory cytokine expression is associated with elevated pain scores in patients with symptomatic TDH. On the other hand, there is no conclusive correlation between the intensity of pain and the local or systemic presence of amino acids associated with pain transmission. (C) 2018 Elsevier Inc. All rights reserved.

BACKGROUND: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves quality of life (QoL), motor, and non-motor symptoms (NMS) in advanced Parkinson's disease (PD). However, considerable inter-individual variability has been observed for QoL outcome.HYPOTHESIS: We hypothesized that demographic and preoperative NMS characteristics can predict postoperative QoL outcome.METHODS: In this ongoing, prospective, multicenter study (Cologne, Manchester, London) including 88 patients, we collected the following scales preoperatively and on follow-up 6 months postoperatively: PDQuestionnaire-8 (PDQ-8), NMSScale (NMSS), NMSQuestionnaire (NMSQ), Scales for Outcomes in PD (SCOPA)-motor examination, -complications, and -activities of daily living, levodopa equivalent daily dose. We dichotomized patients into "QoL responders"/"non-responders" and screened for factors associated with QoL improvement with (1) Spearman-correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions using aforementioned "responders/non-responders" as dependent variable.RESULTS: All outcomes improved significantly on follow-up. However, approximately 44% of patients were categorized as "QoL non-responders". Spearman-correlations, linear and logistic regression analyses were significant for NMSS and NMSQ but not for SCOPA-motor examination. Post-hoc, we identified specific NMS (flat moods, difficulties experiencing pleasure, pain, bladder voiding) as significant contributors to QoL outcome.CONCLUSIONS: Our results provide evidence that QoL improvement after STN-DBS depends on preoperative NMS characteristics. These findings are important in the advising and selection of individuals for DBS therapy. Future studies investigating motor and non-motor PD clusters may enable stratifying QoL outcomes and help predict patients' individual prospects of benefiting from DBS.

Objectives The aim of this study was to evaluate the reduction of artifacts from deep brain stimulation electrodes (DBS) using an iterative metal artifact reduction algorithm (O-MAR), virtual monoenergetic images (VMI), and both in combination in postoperative spectral detector computed tomography using a dual-layer detector (spectral detector computed tomography [SDCT]) of the head. Material and methods Nonanthropomorphic phantoms with different DBS leads were examined on SDCT; in 1 phantom periprocedural bleeding was simulated. A total of 20 patients who underwent SDCT after DBS implantation between October 2016 and April 2017 were included in this institutional review board-approved retrospective study. Images were reconstructed using standard-of-care iterative reconstruction (CI) and VMI, each with and without O-MAR processing (IR and MAR). Artifacts were quantified by determining the percentage integrity uniformity in an annular region of 1.4 cm around the DBS lead; a percentage integrity uniformity of 100% indicates the absence of artifacts. In phantoms, conspicuity of blood was determined on a binary scale, whereas in patients, image quality, DBS lead assessment, and extent of artifact reduction were assessed on Likert scales by 2 radiologists. Statistical significance was assessed using analysis of variance and Wilcoxon tests; sensitivity and specificity were calculated. Results The O-MAR processing significantly decreased artifacts in phantom and patients (P ≤ 0.05), whereas VMI did not reduce artifact burden compared with corresponding CI (P > 0.05): for example, CI-IR/MAR and 200 keV-IR/MAR for patients: 76.3%/90.7% and 75.9%/91.2%, respectively. Qualitatively, overall image quality was not improved (P > 0.05) and MAR improved DBS assessment (CI-IR/MAR: 2 [1-3]/3 [2-4]; P ≤ 0.05) and reduced artifacts significantly (P ≤ 0.05). The O-MAR processing increased sensitivity for bleeding by 160%. In some cases, new artifacts were induced through O-MAR processing, none of which impaired diagnostic image assessment. Discussion The investigated O-MAR algorithm reduces artifacts from DBS electrodes and should be used in the assessment of postoperative patients; however, combination with VMI does not provide an additional benefit.

Background The objective of this study was to investigate 24-month of effects of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on nonmotor symptoms in Parkinson's disease (PD). Methods In this prospective, observational, multicenter, international study including 67 PD patients undergoing bilateral STN-DBS, we examined the Non-motor Symptom Scale, Non-Motor Symptoms Questionnaire, Parkinson's Disease Questionnaire-8, Scales for Outcomes in Parkinson's Disease-motor examination, -activities of daily living, and -complications, and levodopa-equivalent daily dose preoperatively and at 5 and 24-month of follow-up. After checking distribution normality, longitudinal outcome changes were investigated with Friedman tests or repeated-measures analysis of variance and Bonferroni correction for multiple comparisons using multiple tests. Post hoc, Wilcoxon signed rank t tests were computed to compare visits. The strength of clinical responses was analyzed using effect size. Explorative Spearman correlations of change scores from baseline to 24-month follow-up were calculated for all outcomes. Results The Non-motor Symptom Scale and all other outcome parameters significantly improved from baseline to the 5-month follow-up. From 5 to 24-month, partial decrements in these gains were found. Nonetheless, comparing baseline with 24-month follow-up, significant improvements were observed for the Non-motor Symptom Scale (small effect), Scales for Outcomes in PD-motor examination showed a moderate effect, and Scales for Outcomes in Parkinson's Disease-complications and levodopa-equivalent daily dose showed large effects. Non-motor Symptom Scale change scores from baseline to 24-month follow-up correlated significantly with Parkinson's Disease Questionnaire-8, Scales for Outcomes in Parkinson's Disease-activities of daily living, and -motor complications change scores. Conclusions This study provides evidence of beneficial effects of bilateral STN-DBS on nonmotor symptoms at 24-month follow-up. The extent of nonmotor symptom improvement was directly proportionate to improvements in quality of life, activities of daily living, and motor complications. This study underlines the importance of nonmotor symptoms for holistic assessments of DBS outcomes. © 2018 International Parkinson and Movement Disorder Society.

Objectives First reports on the application of deep brain stimulation (DBS) of the Nucleus basalis of Meynert (NBM) showed feasibility and safety of the intervention in patients with Alzheimer´s disease. However, clinical effects vary and the mechanisms of actions are still not well understood. The aim of this study was to characterize neuroimaging changes that are associated with the responsiveness to the treatment. Materials and Methods We examined preoperative T1-weighted MR images of ten patients with Alzheimer's disease (AD) treated with DBS of the NBM and correlated the clinical outcome with volumetric differences of cortical thickness. Subsequently, we sought to identify brain regions that carry out the clinical effects by correlating the outcome with streamlines connected to the volume of activated tissue. Clinical assessments at baseline, 6 and 12 months after the intervention included the AD Assessment Scale as well as the mini mental status examination. Results A fronto-parieto-temporal pattern of cortical thickness was found to be associated with beneficial outcome. Modulation of streamlines connected to left parietal and opercular cortices was associated with better response to the intervention. Conclusion Our results indicate that patients with less advanced atrophy may profit from DBS of the NBM. We conclude that beneficial effects of the intervention are related to preserved fronto-parieto-temporal interplay.

Background Deep brain stimulation (DBS) of the subcallosal cingulate gyrus (SCG) is an experimental approach in treatment-resistant depression (TRD). Short-term results of efficacy in DBS are incongruent and studies investigating long-term effects are warranted. Methods We assessed efficacy of SCG-DBS in eight patients randomized into a delayed-onset group (sham-DBS four weeks) and a non-delayed-onset group. The primary outcome measure was improvement on the Hamilton Depression Rating-Scale (HAMD-24-item-version). Response was defined as HAMD-24 reduction of at least 50% compared to baseline. Assessment was double-blind for a period of eight weeks and after 6,- 12,- 24,- and 28,- months open-label. Results The average improvement in HAMD-24 scores after 6,- 12,- and 24-months were 34%, 25%, and 37%. After 6 months, HAMD-24 revealed a significant difference (P = .022) and 37.5% of the patients were responders. After 12 months, HAMD-24 scores dropped, but no significant difference was observed. After 24 months, a significant improvement was found (P = .041). After the four weeks lasting sham vs. DBS-ON period, there was no group difference (P = .376) in HAMD-24 and patients did not improve during sham stimulation. Patients were followed until 28 months and two up to 4 years under SCG-DBS and average response rate was 51%, whereas two patients were remitters (33,3%). Limitations The small sample size limited the statistical power and external validity. Conclusions Long-term improvement after SCG-DBS revealed a stable effect. There was no significant difference in response rates between the delayed and non-delayed-onset group. DBS for TRD remains experimental and longitudinal investigations of large samples are needed.

Objective Thalamic deep brain stimulation (DBS) is effective in reducing tics in patients with refractory Tourette syndrome at the short-term. Here, we report on the long-term outcome. Materials and Methods Seven patients underwent bilateral DBS between 2001 and 2008. The target was the centromedian nucleus, substantia periventricularis and nucleus ventro-oralis internus cross point of the thalamus. The effect on tics and side effects were evaluated with a variable follow-up duration of 12 to 78 months. Results Patient 1 and 2 showed good tic improvements of 81.6% (60 months) and 50% (36 months), respectively. However, side effects like reducing levels of energy and visual disturbances increased. In patient 1, the target was changed to the anterior part of the internal pallidum and patient 2 switched the stimulator permanently off. Patient 3 experiences still satisfying results with a tic improvement of 88.9% (78 months). Patient 4 and 7 showed minor tic improvements of 34% (16 months) and 9% (60 months), respectively. In both patients side effects became more severe and the target was changed to the anterior part of the internal pallidum. Patient 5 showed a tic improvement of 27.5% (12 months) and went abroad for stimulation of the external globus pallidus. Patient 6 developed cerebellar atrophy. He experienced several nonstimulation related side effects and turned the stimulator off. Conclusions There seems to be an increasing disbalance of therapeutic effects and side effects at long-term follow-up, often leading to either switching the stimulator off or new surgery with a different neuro-anatomic target.

The Movement Disorder Society recommends the Bain and Findley Tremor ADL Scale to assess ADL in patients with ET. In 45 medically and 14 surgically (DBS) treated ET patients, a German version of the scale correlated well with tremor severity and quality of life and was sensitive to postoperative change.

Background Stimulation parameters in deep brain stimulation (DBS) of the subthalamic nucleus for Parkinson's disease (PD) are rarely tested in double-blind conditions. Evidence-based recommendations on optimal stimulator settings are needed. Results from the CUSTOM-DBS study are reported, comparing 2 pulse durations. Methods A total of 15 patients were programmed using a pulse width of 30 µs (test) or 60 µs (control). Efficacy and side-effect thresholds and unified PD rating scale (UPDRS) III were measured in meds-off (primary outcome). The therapeutic window was the difference between patients' efficacy and side effect thresholds. Results The therapeutic window was significantly larger at 30 µs than 60 µs (P = ·0009) and the efficacy (UPDRS III score) was noninferior (P = .00008). Interpretation Subthalamic neurostimulation at 30 µs versus 60 µs pulse width is equally effective on PD motor signs, is more energy efficient, and has less likelihood of stimulation-related side effects. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.