Incidence and Management of Hardware-Related Wound Infections in Spinal Cord, Peripheral Nerve Field, and Deep Brain Stimulation Surgery: A Single-Center Study.

INTRODUCTION: Neuromodulation using deep brain stimulation (DBS), spinal cord stimulation (SCS), and peripheral nerve field stimulation (PNFS) to treat neurological, psychiatric, and pain disorders is a rapidly growing field. Infections related to the implanted hardware are among the most common complications and result in health-related and economic burden. Unfortunately, conservative medical therapy is less likely to be successful. In this retrospective study, we aimed to identify characteristics of the infections and investigated surgical and antimicrobial treatments. METHODS: A retrospective analysis was performed of patients with an infection related to DBS, SCS, and/or PNFS hardware over an 8-year period at our institution. Data were analyzed for type of neurostimulator, time of onset of infection following the neurosurgical procedure, location, and surgical treatment strategy. Surgical treatment of infections consisted of either a surgical wound revision without hardware removal or a surgical wound revision with partial or complete hardware removal. Data were further analyzed for the microorganisms involved, antimicrobial treatment and its duration, and clinical outcome. RESULTS: Over an 8-year period, a total of 1,250 DBS, 1,835 SCS, and 731 PNFS surgeries were performed including de novo system implantations, implanted pulse generator (IPG) replacements, and revisions. We identified 82 patients with infections related to the neurostimulator hardware, representing an incidence of 3.09% of the procedures. Seventy-one percent of the patients had undergone multiple surgeries related to the neurostimulator prior to the infection. The infections occurred after a mean of 12.2 months after the initial surgery. The site of infection was most commonly around the IPG, especially in DBS and SCS. The majority (62.2%) was treated by surgical wound revision with simultaneous partial or complete removal of hardware. Microbiological specimens predominantly yielded Staphylococcus epidermidis (39.0%) and Staphylococcus aureus (35.4%). After surgery, antimicrobials were given for a mean of 3.4 weeks. The antimicrobial regime was significantly shorter in patients with hardware removal in comparison to those who only had undergone surgical wound revision. One intracranial abscess occurred. No cases of infection-related death, sepsis, bacteremia, or intraspinal abscesses were found. CONCLUSION: Our data did show the predominance of S. epidermidis and S. aureus as etiologic organisms in hardware-related infections. Infections associated with S. aureus most likely required (partial) hardware removal. Aggressive surgical treatment including hardware removal shortens the duration of antimicrobial treatment. Clear strategies should be developed to treat hardware-related infections to optimize patient management and reduce health- and economic-related burden.

Pallidal deep brain stimulation in a patient with nonketotic hyperglycemic hemichorea.

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.

Brain Morphometry Associated With Response to Levodopa and Deep Brain Stimulation in Parkinson Disease.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Connectivity in deep brain stimulation for self-injurious behavior: multiple targets for a common network?

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.

Accuracy of Robotic and Frame-Based Stereotactic Neurosurgery in a Phantom Model.

Background: 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. Methods: 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. Results: 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 (p < 0.05). In robotics, the mean depth deviation along the trajectory was -0.22 mm (95% CI -0.25 to -0.14 mm). The mean lateral deviation was 0.43 mm (95% CI 0.32-0.49 mm). In frame-based stereotaxy, the mean depth deviation amounted to -0.20 mm (95% CI -0.26 to -0.14 mm), the mean lateral deviation to 0.65 mm (95% CI 0.55-0.74 mm). Conclusion: 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.

Gender gap in deep brain stimulation for Parkinson's disease.

Previous studies have shown less access to deep brain stimulation (DBS) for Parkinson's disease (PD) in women compared to men raising concerns about a potential gender gap resulting from nonclinical factors or gender differences in clinical efficacy for postoperative quality of life (QoL), motor, and nonmotor symptoms (NMS) outcomes. This was a cross-sectional and a longitudinal, prospective, observational, controlled, quasi-experimental, international multicenter study. A total sample size of 505 consisted of 316 consecutively referred patients for DBS indication evaluation at the University Hospital Cologne (01/2015-09/2020) and 189 consecutively treated patients at DBS centers in the University Hospitals Cologne and Marburg, Salford's Royal Hospital Manchester, and King's College Hospital London. In the cross-sectional cohort, we examined gender proportions at referral, indication evaluations, and DBS surgery. In the longitudinal cohort, clinical assessments at preoperative baseline and 6-month follow-up after surgery included the PD Questionnaire-8, NMSScale, Scales for Outcomes in PD-motor scale, and levodopa-equivalent daily dose. Propensity score matching resulted in a pseudo-randomized sub-cohort balancing baseline demographic and clinical characteristics between women with PD and male controls. 316 patients were referred for DBS. 219 indication evaluations were positive (women n = 102, respectively n = 82). Women with PD were disproportionally underrepresented in referrals compared to the general PD population (relative risk [RR], 0.72; 95%CI, 0.56-0.91; P = 0.002), but more likely to be approved for DBS than men (RR, 1.17; 95%CI, 1.03-1.34; P = 0.029). Nonetheless, their total relative risk of undergoing DBS treatment was 0.74 (95%CI, 0.48-1.12) compared to men with PD. At baseline, women had longer disease duration and worse dyskinesia. Exploring QoL domains, women reported worse mobility and bodily discomfort. At follow-up, all main outcomes improved equally in both genders. Our study provides evidence of a gender gap in DBS for PD. Women and men with PD have distinct preoperative nonmotor and motor profiles. We advocate that more focus should be directed toward the implementation of gender equity as both genders benefit from DBS with equal clinical efficacy. This study provides Class II evidence of beneficial effects of DBS in women with PD compared to male controls.

Radiomics outperforms semantic features for prediction of response to stereotactic radiosurgery in brain metastases.

BACKGROUND: Brain metastases show different patterns of contrast enhancement, potentially reflecting hypoxic and necrotic tumor regions with reduced radiosensitivity. An objective evaluation of these patterns might allow a prediction of response to radiotherapy. We therefore investigated the potential of MRI radiomics in comparison with the visual assessment of semantic features to predict early response to stereotactic radiosurgery in patients with brain metastases. PATIENTS AND METHODS: In this retrospective study, 150 patients with 308 brain metastases from solid tumors (NSCLC in 53% of patients) treated by stereotactic radiosurgery (single dose of 17-20 Gy) were evaluated. The response of each metastasis (partial or complete remission vs. stabilization or progression) was assessed within 180 days after radiosurgery. Patterns of contrast enhancement in the pre-treatment T1-weighted MR images were either visually classified (homogenous, heterogeneous, necrotic ring-like) or subjected to a radiomics analysis. Random forest models were optimized by cross-validation and evaluated in a hold-out test data set (30% of metastases). RESULTS: In total, 221/308 metastases (72%) responded to radiosurgery. The optimal radiomics model comprised 10 features and outperformed the model solely based on semantic features in the test data set (AUC, 0.71 vs. 0.56; accuracy, 69% vs. 54%). The diagnostic performance could be further improved by combining semantic and radiomics features resulting in an AUC of 0.74 and an accuracy of 75% in the test data set. CONCLUSION: The developed radiomics model allowed prediction of early response to radiosurgery in patients with brain metastases and outperformed the visual assessment of patterns of contrast enhancement.

Frame-based stereotactic implantation of cystoventricular shunts for treating acquired intracerebral cysts.

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.

Thalamic deep brain stimulation for Tourette Syndrome: A naturalistic trial with brief randomized, double-blinded sham-controlled periods.

BACKGROUND: There is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome. OBJECTIVES: In this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation. METHODS: We included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six- and twelve-months' assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety. RESULTS: Active stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label-phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae. CONCLUSION: Our results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome.

Performance monitoring in obsessive-compulsive disorder: Insights from internal capsule/nucleus accumbens deep brain stimulation.

BACKGROUND: Symptoms of obsessive-compulsive disorder (OCD) are partly related to impaired cognitive control processes and theta modulations constitute an important electrophysiological marker for cognitive control processes such as signaling negative performance feedback in a fronto-striatal network. Deep brain stimulation (DBS) targeting the anterior limb of the internal capsule (ALIC)/nucleus accumbens (NAc) shows clinical efficacy in OCD, while the exact influence on the performance monitoring system remains largely unknown. METHODS: Seventeen patients with treatment-refractory OCD performed a probabilistic reinforcement learning task. Analyses were focused on 4-8 Hz (theta) power, intertrial phase coherence (ITPC) and debiased weighted Phase-Lag Index (dwPLI) in response to negative performance feedback. Combined EEG and local field potential (LFP) recordings were obtained shortly after DBS electrode implantation to investigate fronto-striatal network modulations. To assess the impact of clinically effective DBS on negative performance feedback modulations, EEG recordings were obtained pre-surgery and at follow-up with DBS on and off. RESULTS: Medial frontal cortex ITPC, striatal ITPC and striato-frontal dwPLI were increased following negative performance feedback. Decreased right-lateralized dwPLI was associated with pre-surgery symptom severity. ITPC was globally decreased during DBS-off. CONCLUSION: We observed a theta phase coherence mediated fronto-striatal performance monitoring network. Within this network, decreased connectivity was related to increased OCD symptomatology, consistent with the idea of impaired cognitive control in OCD. While ALIC/NAc DBS decreased theta network activity globally, this effect was unrelated to clinical efficacy and performance monitoring.

Radiomics for prediction of radiation-induced lung injury and oncologic outcome after robotic stereotactic body radiotherapy of lung cancer: results from two independent institutions.

OBJECTIVES: To generate and validate state-of-the-art radiomics models 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: Radiomics models were 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, 199 uncorrelated radiomic features fulfilling the standards of the Image Biomarker Standardization Initiative (IBSI) were extracted from the outlined gross tumor volume (GTV). Regularized models (Coxnet and Gradient Boost) for the development of local lung fibrosis (LF), local tumor control (LC), disease-free survival (DFS) and overall survival (OS) were built from either clinical/ dosimetric variables, radiomics features or a combination thereof and 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 significantly 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, radiomics models were able to predict OS, DFS and LC (concordance index 0.77-0.99, p < 0.005), but failed to generalize to the test cohort. In opposite, models for the development of lung fibrosis could be generated from both clinical/dosimetric factors and radiomic features or combinations thereof, which were both predictive in the training set (concordance index 0.71- 0.79, p < 0.005) and in the test set (concordance index 0.59-0.66, p < 0.05). The best performing model included 4 clinical/dosimetric variables (GTV-Dmean, PTV-D95%, Lung-D1ml, age) and 7 radiomic features (concordance index 0.66, p < 0.03). CONCLUSION: Despite the obvious difficulties in generalizing predictive models for oncologic outcome and toxicity, this analysis shows that carefully designed radiomics models for prediction of local lung fibrosis after SBRT of early stage lung cancer perform well across different institutions.

1.2 kHz High-Frequency Stimulation as a Rescue Therapy in Patients With Chronic Pain Refractory to Conventional Spinal Cord Stimulation.

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.

Modulation of Fibers to Motor Cortex during Thalamic DBS in Tourette Patients Correlates with Tic Reduction.

Probabilistic tractography in Tourette syndrome (TS) patients have shown an alteration in the connectivity of the primary motor cortex and supplementary motor area with the striatum and thalamus, suggesting an abnormal connectivity of the cortico-striatum-thalamocortical-pathways in TS. Deep brain stimulation (DBS) of the centromedian nucleus-nucleus ventrooralis internus (CM-Voi complex) in the thalamus is an effective treatment for refractory TS patients. We investigated the connectivity of activated fibers from CM-Voi to the motor cortex and its correlation between these projections and their clinical outcome. Seven patients with TS underwent CM-Voi-DBS surgery and were clinically evaluated preoperatively and six months postoperatively. We performed diffusion tensor imaging to display the activated fibers projecting from the CM-Voi to the different motor cortex regions of interest. These analyses showed that the extent of tic reduction during DBS is associated with the degree of stimulation-dependent connectivity between CM-Voi and the motor cortex, and in particular, an increased density of projections to the presupplementary motor area (preSMA). Non-responder patients displayed the largest amount of active fibers projecting into cortical areas other than motor cortex compared to responder patients. These findings support the notion that an abnormal connectivity of thalamocortical pathways underlies TS, and that modulation of these circuits through DBS could restore the function and reduce symptoms.

Volumetric Analysis of the Pterygopalatine Fossa by Semiautomatic Segmentation of Cone Beam Computed Tomography.

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.

Deep convolutional neural networks for automated segmentation of brain metastases trained on clinical data.

INTRODUCTION: Deep learning-based algorithms have demonstrated enormous performance in segmentation of medical images. We collected a dataset of multiparametric MRI and contour data acquired for use in radiosurgery, to evaluate the performance of deep convolutional neural networks (DCNN) in automatic segmentation of brain metastases (BM). METHODS: A conventional U-Net (cU-Net), a modified U-Net (moU-Net) and a U-Net trained only on BM smaller than 0.4 ml (sU-Net) were implemented. Performance was assessed on a separate test set employing sensitivity, specificity, average false positive rate (AFPR), the dice similarity coefficient (DSC), Bland-Altman analysis and the concordance correlation coefficient (CCC). RESULTS: A dataset of 509 patients (1223 BM) was split into a training set (469 pts) and a test set (40 pts). A combination of all trained networks was the most sensitive (0.82) while maintaining a specificity 0.83. The same model achieved a sensitivity of 0.97 and a specificity of 0.94 when considering only lesions larger than 0.06 ml (75% of all lesions). Type of primary cancer had no significant influence on the mean DSC per lesion (p = 0.60). Agreement between manually and automatically assessed tumor volumes as quantified by a CCC of 0.87 (95% CI, 0.77-0.93), was excellent. CONCLUSION: Using a dataset which properly captured the variation in imaging appearance observed in clinical practice, we were able to conclude that DCNNs reach clinically relevant performance for most lesions. Clinical applicability is currently limited by the size of the target lesion. Further studies should address if small targets are accurately represented in the test data.

Left Prefrontal Connectivity Links Subthalamic Stimulation with Depressive Symptoms.

OBJECTIVE: Subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) not only stimulates focal target structures but also affects distributed brain networks. The impact this network modulation has on non-motor DBS effects is not well-characterized. By focusing on the affective domain, we systematically investigate the impact of electrode placement and associated structural connectivity on changes in depressive symptoms following STN-DBS, which have been reported to improve, worsen, or remain unchanged. METHODS: Depressive symptoms before and after STN-DBS surgery were documented in 116 patients with PD from 3 DBS centers (Berlin, Queensland, and Cologne). Based on individual electrode reconstructions, the volumes of tissue activated (VTAs) were estimated and combined with normative connectome data to identify structural connections passing through VTAs. Berlin and Queensland cohorts formed a training and cross-validation dataset used to identify structural connectivity explaining change in depressive symptoms. The Cologne data served as the test-set for which depressive symptom change was predicted. RESULTS: Structural connectivity was linked to depressive symptom change under STN-DBS. An optimal connectivity map trained on the Berlin cohort could predict changes in depressive symptoms in Queensland patients and vice versa. Furthermore, the joint training-set map predicted changes in depressive symptoms in the independent test-set. Worsening of depressive symptoms was associated with left prefrontal connectivity. INTERPRETATION: Fibers connecting the electrode with left prefrontal areas were associated with worsening of depressive symptoms. Our results suggest that for the left STN-DBS lead, placement impacting fibers to left prefrontal areas should be avoided to maximize improvement of depressive symptoms. ANN NEUROL 2020;87:962-975.

PET/MRI Radiomics in Patients With Brain Metastases.

Although a variety of imaging modalities are used or currently being investigated for patients with brain tumors including brain metastases, clinical image interpretation to date uses only a fraction of the underlying complex, high-dimensional digital information from routinely acquired imaging data. The growing availability of high-performance computing allows the extraction of quantitative imaging features from medical images that are usually beyond human perception. Using machine learning techniques and advanced statistical methods, subsets of such imaging features are used to generate mathematical models that represent characteristic signatures related to the underlying tumor biology and might be helpful for the assessment of prognosis or treatment response, or the identification of molecular markers. The identification of appropriate, characteristic image features as well as the generation of predictive or prognostic mathematical models is summarized under the term radiomics. This review summarizes the current status of radiomics in patients with brain metastases.

PSA and VIM DBS efficiency in essential tremor depends on distance to the dentatorubrothalamic tract.

OBJECTIVE: To investigate the relation between deep brain stimulation (DBS) of the posterior-subthalamic-area (PSA) and the ventral-intermediate-nucleus (VIM) and the distance to the dentatorubrothalamic tract (DRTT) in essential tremor (ET). METHODS: Tremor rating scale (TRS) hemi-scores were analyzed in 13 ET patients, stimulated in both the VIM and the PSA in a randomized, crossover trial. Distances of PSA and VIM contacts to population-based DRTTs were calculated. The relationships between distance to DRTT and stimulation amplitude, as well as DBS efficiency (TRS improvement per amplitude) were investigated. RESULTS: PSA contacts were closer to the DRTT (p = 0.019) and led to a greater improvement in TRS hemi-scores (p = 0.005) than VIM contacts. Proximity to the DRTT was related to lower amplitudes (p < 0.001) and higher DBS efficiency (p = 0.017). CONCLUSIONS: Differences in tremor outcome and stimulation parameters between contacts in the PSA and the VIM can be explained by their different distance to the DRTT.

Characterization of information processing in the subthalamic area of Parkinson's patients.

Despite advances in symptomatic treatment options the pathomechanism of idiopathic Parkinson's disease (PD) remains poorly understood. Animal studies from recent years suggest pathological information processing in the basal ganglia network to be responsible for major movement deficits observed in patients, which, according to the information lesion hypothesis, might also explain the mechanism of action of deep brain stimulation (DBS). Using novel measures from information theory we characterize the information content, storage and transfer of intraoperatively recorded local field potentials (LFP) from the subthalamic area of n â€‹= â€‹19 PD patients undergoing surgery for implantation of electrodes for deep brain stimulation. In agreement with recent animal studies we demonstrate a significant positive correlation of subthalamic information content and movement deficits (ρ â€‹> â€‹0.48). Analysis of information storage reveals a larger processing memory in the zona incerta (ZI) than in the subthalamic nucleus (STN). We discuss possible implications for the efficiency of high frequency DBS. Further, we estimate the information transfer between forearm muscles and ZI/STN. Here, we show that the bidirectional information flow with respect to the STN is larger compared to the ZI. In contrast to the STN, however, the bidirectional information flow in the ZI is modulated, namely increased, by movement. The results of our study may help to understand the mechanism of action of deep brain stimulation and further explain recent studies claiming efficiency of ZI stimulation for certain motor symptoms.

The effects of thalamic and posterior subthalamic deep brain stimulation on speech in patients with essential tremor - A prospective, randomized, doubleblind crossover study.

OBJECTIVE: To prospectively evaluate the effect of PSA- and VIM DBS on speech in ET patients. METHODS: Leads were implanted bilaterally with contacts placed in both VIM and PSA. Thirteen patients were analyzed pre- and postoperatively. Preoperative speech of ET patients was compared to healthy controls. PSA- and VIM-DBS were evaluated in a randomized, double-blind crossover phase. RESULTS: At preoperative baseline, we found reduced intelligibility. Differences in acoustic and VAS data ('ability to speak') compared to controls were gradient. Articulation rate could be predicted by disease duration. Decreased articulation rate, spirantization and voicing were found for PSA- and VIM-DBS. Targets did not differ in terms of speech deterioration. CONCLUSION: Speech in ET patients without DBS can be impaired, dependent on patient's individual characteristics. Both PSA- and VIM-DBS affect speech in a comparable way. Thus, the PSA can be considered an alternative DBS target in ET without higher risk of dysarthria.