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Background: Cancer is commonly associated with pain. For patients with advanced cancer and intractable pain, ablative neurosurgical procedures can significantly improve pain and transition patients out of inpatient settings. These procedures are normally invasive, and this poses an important risk in this population. Cingulotomy has been reported to improve pain perception and contribute substantially to the quality of life of cancer patients with refractory pain., Observations: One fresh human cadaver specimen was used for the setup. The cingulate gyrus was targeted using intraoperative magnetic resonance images, and osseous aberrations were corrected after coregistration with the preoperative head computed tomography. After accounting for sinuses, membrane folds, and calcifications, a total of 737 elements were available for thermal ultrasound ablation. On high-power sonications, the total energy delivered reached a peak temperature of 57°C (15,050 J, 350 W, 45 seconds) in the right cingulate and 52°C (13,000 J, 405 W, 46 seconds) in the left cingulate., Lessons: Despite the limitations of using a cadaver model (temperature, vascularization), cingulotomy appears to be feasible using high-intensity focused ultrasound. https://thejns.org/doi/10.3171/CASE2459.

Neuropathic pain is a chronic condition representing a significant burden for society. It is estimated 1 out of 10 people over the age of 30 that in the US have been diagnosed with neuropathic pain. Most of the available treatments for neuropathic pain have moderate efficacy over time which limit their use; therefore, other therapeutic approaches are needed for patients. Spinal cord stimulation is an established and cost-effective modality for treating severe chronic pain. In this article we will review the current approved indications for the use of spinal cord stimulation in the US and the novel therapeutic options which are now available using this therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Periprosthetic joint infection (PJI) poses a challenging complication for many patients undergoing arthroplasty, and the literature identifies numerous risk factors. A comprehensive understanding of the primary risk and protective factors for PJI is valuable for surgeons. This article aims to compile and summarize the key risk factors for PJI documented in the literature. Some risk factors are related to the nutritional status of patients, with obesity, weight loss, hypovitaminosis, and malnutrition being frequently reported. Pathologies affecting patients also contribute to PJI risk, including septic arthritis, hepatitis, diabetes, urinary tract infections, anemia, hypothyroidism, osteoporosis, and dental pathologies. Unhealthy habits, such as tobacco and drug abuse, are significant factors. Previous corticosteroid injections may also play a role in infection development. A few protective factors are also reported in the literature (use of statins, preoperative decolonization, and preadmission skin preparation). The identification of risk factors and the implementation of evidence-based preoperative protocols are essential steps in reducing the incidence of PJI., Competing Interests: The authors declare no conflicts of interest.

Visceral signals are constantly processed by our central nervous system, enable homeostatic regulation, and influence perception, emotion, and cognition. While visceral processes at the cortical level have been extensively studied using non-invasive imaging techniques, very few studies have investigated how this information is processed at the single neuron level, both in humans and animals. Subcortical regions, relaying signals from peripheral interoceptors to cortical structures, are particularly understudied and how visceral information is processed in thalamic and subthalamic structures remains largely unknown. Here, we took advantage of intraoperative microelectrode recordings in patients undergoing surgery for deep brain stimulation (DBS) to investigate the activity of single neurons related to cardiac and respiratory functions in three subcortical regions: ventral intermedius nucleus (Vim) and ventral caudalis nucleus (Vc) of the thalamus, and subthalamic nucleus (STN). We report that the activity of a large portion of the recorded neurons (about 70%) was modulated by either the heartbeat, the cardiac inter-beat interval, or the respiration. These cardiac and respiratory response patterns varied largely across neurons both in terms of timing and their kind of modulation. A substantial proportion of these visceral neurons (30%) was responsive to more than one of the tested signals, underlining specialization and integration of cardiac and respiratory signals in STN and thalamic neurons. By extensively describing single unit activity related to cardiorespiratory function in thalamic and subthalamic neurons, our results highlight the major role of these subcortical regions in the processing of visceral signals., Competing Interests: Competing interests statement:The authors declare no competing interest.

Abstract: Intra-articular steroid injections for knee osteoarthritis are a routine procedure in musculoskeletal clinics. While their role in osteoarthritis care is debatable, they serve as an important therapeutic option to relieve osteoarthritis-associated pain. Potential risks are self-limited (increased pain flare, local skin irritation, flushing, insomnia) or severe (septic arthritis, intravascular medication placement, and the deleterious effect on cartilage and bone). In our experience, more serious adverse events are rare. In this case, we present a complication secondary to intra-articular steroid administration that has not previously been reported in the literature: superficial vein thrombosis. This will raise awareness among clinicians, improve the informed consent process, and provide an approach for the management of subsequent injections., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Interdisciplinary teamwork is essential for the rehabilitation of patients with cleft lip and palate, and therefore, the application of treatment techniques for velopharyngeal insufficiency, both surgical and prosthetic, depends on the experience of each rehabilitation team. For this reason, the following study consisting of the cooperation between interdisciplinary cleft lip and palate teams from Chile and Argentina, which succeeded in correcting velopharyngeal insufficiency in an adolescent, initially using a pharyngeal bulb prosthesis and speech therapy, and finally through pharyngeal flap surgery, is presented. This shows that international cooperation is a valuable tool for training, implementation, and follow-up of different treatment techniques for teams in formation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Objective: Focused ultrasound ablation (FUSA) is an emerging treatment for neurological and psychiatric diseases. We describe the initial experience from a pilot, open-label, single-center clinical trial of unilateral anterior nucleus of the thalamus (ANT) FUSA in patients with treatment-refractory epilepsy., Methods: Two adult subjects with treatment-refractory, focal onset epilepsy were recruited. The subjects received ANT FUSA using the Exablate Neuro (Insightec) system. We determined the safety and feasibility (primary outcomes), and changes in seizure frequency (secondary outcome) at 3, 6, and 12 months. Safety was assessed by the absence of side effects, that is, new onset neurological deficits or performance deterioration on neuropsychological testing. Feasibility was defined as the ability to create a lesion within the anterior nucleus. The monthly seizure frequency was compared between baseline and postthalamotomy., Results: The patients tolerated the procedure well, without neurological deficits or serious adverse events. One patient experienced a decline in verbal fluency, attention/working memory, and immediate verbal memory. Seizure frequency reduced significantly in both patients; one patient was seizure-free at 12 months, and in the second patient, the frequency reduced from 90-100 seizures per month to 3-6 seizures per month., Significance: This is the first known clinical trial to assess the safety, feasibility, and preliminary efficacy of ANT FUSA in adult patients with treatment-refractory focal onset epilepsy., (© 2023 International League Against Epilepsy.)

The current white matter connectivity analyses of the subthalamic region have focused on the motor effects of deep brain stimulation. We investigate white matter connectivity associated with the stimulation-induced non-motor acute clinical effects in three domains: mood changes, dizziness, and sweating. We performed whole-brain probabilistic tractography seeded from the domain-specific stimulation volumes. The resultant connectivity maps were statistically compared across patients. The cortical voxels associated with each non-motor domain were compared with stimulation-induced motor improvements in a multivariate model. The resulting voxel maps were thresholded for false discovery (FDR q < 0.05) and clustered using a multimodal atlas. We also performed a group-level parcellation of stimulation volumes to identify the local pathways associated with each non-motor domain. The non-motor effects were rarely observed during stimulation titration: from 1100 acute clinical effects, mood change was observed in 14, dizziness in 23, and sweating in 20. Distinct cortical clusters were associated with each domain; notably, mood change was associated with voxels in the salience network and dizziness with voxels in the visual association cortex. The subthalamic parcellation yielded a mediolateral gradient, with the motor parcel being lateral and the non-motor parcels medial. We also observed an anteroposterior organization in the medial non-motor clusters with mood changes being anterior, followed posteriorly by dizziness, and sweating. We interpret these findings based on the literature and foresee these to be useful in guiding DBS programming., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hemorrhagic Cholecystitis is a rare condition and usually represents a complication of acute cholecystitis. The clinical presentation is quite overlapping and usually involves abdominal pain that may be associated with fever, jaundice, nausea, vomiting, and finally haemobilia. It frequently involves patients with preexisting conditions such as chronic kidney disease undergoing hemodialysis or anticoagulation therapy. Due to the deadly potential of this condition attention must be high during diagnostics and treatment in order to avoid an ill-fated conclusion. To our knowledge, there is a lack of a comprehensive review on the subject as most of the literature consists of case reports or small case series. In order to give a contribution to improving the treatment strategy of this condition, we report a case successfully treated with cholecystectomy, and performed a literature review. Using the term "Hemorrhagic Cholecystitis", on PubMed database we found 67 cases reported in the English literature. The cases were analyzed by two researchers and clinical information was extrapolated and organized, aiming to create a comprehensive review on the subject, that may be clear and useful in clinical practice. KEY WORDS: Hemorrhagic cholecystitis, Surgical treatment.

Objective: Outcomes after focused ultrasound ablation (FUSA) for essential tremor remain heterogeneous, despite therapeutic promise. Clinical outcomes are directly related to the volume and location of the therapeutic lesions, consistent with CNS ablative therapies. Recent data demonstrate that postoperative diffusion MRI, specifically the quantification of intracellular diffusion by restricted diffusion imaging (RDI), can accurately characterize focused ultrasound lesions. However, it is unclear whether RDI can reliably detect focused ultrasound lesions intraoperatively (i.e., within a few minutes of lesioning) and whether the intraoperative lesions predict delayed clinical outcomes., Methods: An intraoperative imaging protocol was implemented that included RDI and T2-weighted imaging in addition to intraoperative MR thermography. Lesion characteristics were defined with each sequence and then compared. An imaging-outcomes analysis was performed to determine lesion characteristics associated with delayed clinical outcomes., Results: Intraoperative RDI accurately identified the volume and location of focused ultrasound lesions. Intraoperative T2-weighted imaging underestimated the lesion volume but accurately identified the location. Intraoperative RDI revealed that lesions of the ventral border of the ventral intermediate nucleus were significantly associated with postoperative tremor improvement. In contrast, the lesions extending into the inferolateral white matter were associated with postoperative ataxia., Conclusions: These data support the acquisition of intraoperative RDI to characterize focused ultrasound lesions. Future research should test the histological correlates of intraoperative RDI and test whether it can be developed as feedback to optimize the current technique of FUSA.

Objective: Globus pallidus (GP) lesioning improves motor symptoms of Parkinson's disease (PD) and is occasionally associated with nonmotor side effects. Although these variable clinical effects were shown to be site-specific within the GP, the motor and nonmotor subregions have not been distinguished radiologically in patients with PD. The GP was recently found to have a distinct radiological signature on diffusion MRI (dMRI), potentially related to its unique cellular content and organization (or tissue architecture). In this study, the authors hypothesize that the magnitude of water diffusivity, a surrogate for tissue architecture, will radiologically distinguish motor from nonmotor GP subregions in patients with PD. They also hypothesize that the therapeutic focused ultrasound pallidotomy lesions will preferentially overlap the motor subregion., Methods: Diffusion MRI from healthy subjects (n = 45, test-retest S1200 cohort) and PD patients (n = 33) was parcellated based on the magnitude of water diffusivity in the GP, as measured orientation distribution function (ODF). A clustering algorithm was used to identify GP parcels with distinct ODF magnitude. The individual parcels were used as seeds for tractography to distinguish motor from nonmotor subregions. The locations of focused ultrasound lesions relative to the GP parcels were also analyzed in 11 patients with PD., Results: Radiologically, three distinct parcels were identified within the GP in healthy controls and PD patients: posterior, central, and anterior. The posterior and central parcels comprised the motor subregion and the anterior parcel was classified as a nonmotor subregion based on their tractography connections. The focused ultrasound lesions preferentially overlapped with the motor subregion (posterior more than central). The hotspots for motor improvement were localized in the posterior GP parcel., Conclusions: Using a data-driven approach of ODF-based parcellation, the authors radiologically distinguished GP motor subregions in patients with PD. This method can aid stereotactic targeting in patients with PD undergoing surgical treatments, especially focused ultrasound ablation.

Background: During focused ultrasound ablation (FUSA), the presumed stereotactic target is tested with subthreshold sonications before permanent ablation. This testing relies on ultrasound-induced reversible clinical effects (thermal neuromodulation, TN). However, the thermal dose and spot size thresholds to induce TN are not yet defined., Objective: To define the thermal dose and spot size thresholds associated with TN., Methods: We performed a retrospective analysis of intraoperative FUSA data of essential tremor patients. Sonications with a thermal dose of less than 25 cumulative equivalent minutes (CEM) were classified as subthreshold. The intraoperative writing samples were independently rated by 2 raters using the clinical rating scale for tremor. The association between thermal dose and tremor scores was statistically analyzed, and the thermal dose and spot size thresholds for TN were computed using leave-one-out cross-validation analysis., Results: A total of 331 pairs of sonications and writing samples were analyzed; 97 were classified as subthreshold sonications. TN was observed in 23 (24%) subthreshold sonications. The median tremor improvement during TN was 20% (interquartile range = 41.6). The thermal dose threshold for TN was 0.67 CEM (equivalent to 30 s thermal exposure at 43°C). The spot size threshold for TN was 2.46 mm. Ventral intermediate medial nucleus was exposed to TN thermal dose during subablative and ablative sonications., Conclusion: The TN thermal dose and spot size thresholds are significantly higher than the current FUSA standard of care. We recommend long duration (>30 s), subthreshold sonications for intraoperative testing during FUSA. Future investigations should test whether the thermal dose threshold is tissue-specific and determine the mechanisms underlying focused ultrasound TN., (© Congress of Neurological Surgeons 2021.)

Over the last few years, while expanding its clinical indications from movement disorders to epilepsy and psychiatry, the field of deep brain stimulation (DBS) has seen significant innovations. Hardware developments have introduced directional leads to stimulate specific brain targets and sensing electrodes to determine optimal settings via feedback from local field potentials. In addition, variable-frequency stimulation and asynchronous high-frequency pulse trains have introduced new programming paradigms to efficiently desynchronize pathological neural circuitry and regulate dysfunctional brain networks not responsive to conventional settings. Overall, these innovations have provided clinicians with more anatomically accurate programming and closed-looped feedback to identify optimal strategies for neuromodulation. Simultaneously, software developments have simplified programming algorithms, introduced platforms for DBS remote management via telemedicine, and tools for estimating the volume of tissue activated within and outside the DBS targets. Finally, the surgical accuracy has improved thanks to intraoperative magnetic resonance or computerized tomography guidance, network-based imaging for DBS planning and targeting, and robotic-assisted surgery for ultra-accurate, millimetric lead placement. These technological and imaging advances have collectively optimized DBS outcomes and allowed "asleep" DBS procedures. Still, the short- and long-term outcomes of different implantable devices, surgical techniques, and asleep vs. awake procedures remain to be clarified. This expert review summarizes and critically discusses these recent innovations and their potential impact on the DBS field., Competing Interests: AM has received support from the NIH (KL2 TR001426), speaker honoraria from CSL Behring, Abbvie, Abbott, Theravance, and Cynapsus Therapeutics. He has received a salary as chief Editor of Frontiers in Neurology, Experimental Therapeutics, and grant support from Lundbeck and Abbvie. BC has received speaker honoraria from Abbvie. SG is an employee at Medtronic. LR is an employee and shareholder in Newronika, Inc. SP is an employee of Abbott Laboratories. SC is an employee of Boston Scientific. NH is co-founder, and shareholder in Surgical Information Sciences, Inc. VK has received grant support from Medtronic. LV is an editorial board member of Neurology and Therapy, and Brain Sciences. He has received consultant honoraria from Abbott, AbbVie Inc, and Boston Scientific, and research support from Medtronic, Boston Scientific, Abbott, AbbVie, Neuroderm, Biogen Inc. He has received NIH funding (R01 NS40902) as a site-PI. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Merola, Singh, Reeves, Changizi, Goetz, Rossi, Pallavaram, Carcieri, Harel, Shaikhouni, Sammartino, Krishna, Verhagen and Dalm.)

Object: A real-time functional magnetic resonance imaging (fMRI) feedback during ventral intermediate nucleus (VIM) deep brain stimulation (DBS) under general anesthesia (or "asleep" DBS) does not exist. We hypothesized that it was feasible to acquire a reliable and responsive fMRI during asleep VIM DBS surgery. Methods: We prospectively enrolled 10 consecutive patients who underwent asleep DBS for the treatment of medication-refractory essential tremor. Under general anesthesia, we acquired resting-state functional MRI immediately before and after the cannula insertion. Reliability was determined by a temporal signal-to-noise-ratio >100. Responsiveness was determined based on the fMRI signal change upon insertion of the cannula to the VIM. Results: It was feasible to acquire reliable fMRI during asleep DBS surgery. The fMRI signal was responsive to the brain cannula insertion, revealing a reduction in the tremor network's functional connectivity, which did not reach statistical significance in the group analysis. Conclusions: It is feasible to acquire a reliable and responsive fMRI signal during asleep DBS. The acquisition steps and the preprocessing pipeline developed in these experiments will be useful for future investigations to develop fMRI-based feedback for asleep DBS surgery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sammartino, Taylor, Chen, Reynolds, Glen and Krishna.)

Background: Magnetic resonance-guided focused ultrasound thalamotomy (FUS-T) is an emerging treatment for essential tremor (ET)., Objective: To determine the predictors of outcomes after FUS-T., Methods: Two treatment groups were analyzed: 75 ET patients enrolled in the pivotal trial, between 2013 and 2015; and 114 patients enrolled in the postpivotal trials, between 2015 and 2016. All patients had medication-refractory, disabling ET, and underwent unilateral FUS-T. The primary outcome (hand tremor score, 32-point scale with higher scores indicating worse tremor) and the secondary outcome variables (Clinical Rating Scale for Tremor Part C score: 32-point scale with higher scores indicating more disability) were assessed at baseline and 1, 3, 6, and 12 mo. The operative outcome variables (ie, peak temperature, number of sonications) were analyzed. The results between the 2 treatment groups, pivotal and postpivotal, were compared with repeated measures analysis of variance and adjusted for confounding variables., Results: A total of 179 patients completed the 12-mo evaluation. The significant predictors of tremor outcomes were patient age, disease duration, peak temperature, and number of sonications. A greater improvement in hand tremor scores was observed in the postpivotal group at all time points, including 12 mo (61.9% ± 24.9% vs 52.1% ± 24.9%, P = .009). In the postpivotal group, higher energy was used, resulting in higher peak temperatures (56.7 ± 2.5 vs 55.6 ± 2.8°C, P = .004). After adjusting for age, years of disease, number of sonications, and maximum temperature, the treatment group was a significant predictor of outcomes (F = 7.9 [1,165], P = .005)., Conclusion: We observed an improvement in outcomes in the postpivotal group compared to the pivotal group potentially reflecting a learning curve with FUS-T. The other associations of tremor outcomes included patient age, disease duration, peak temperature, and number of sonications., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Introduction: Deep brain stimulation (DBS) is an effective treatment for medically refractory Parkinson's disease (PD). During DBS surgery, intraoperative testing is performed to confirm optimal lead placement by determining the stimulation thresholds for symptom improvement and side effects. However, the reliability of intraoperative testing in predicting distant postoperative thresholds is unknown. In this study, we hypothesized that intraoperative testing reliably estimates postoperative thresholds for both symptom improvement and side effects., Methods: We retrospectively analyzed a prospective database with intraoperative and postoperative thresholds for symptom improvement and side effects from a cohort of 66 PD patients who underwent STN DBS. We recorded the stimulation locations relative to the mid-commissural point. Within-patient stimulation pairs were generated by clustering the intraoperative stimulation locations closest to the DBS contacts. We computed the distance between stimulation locations and atlas-based pyramidal tract (PT) and medial lemniscus (ML) masks. A leave-one-out cross-validation analysis was performed to determine the reliability of intraoperative testing in predicting postoperative thresholds while controlling for the distance from the relevant tracks., Results: Intraoperative testing reliably predicted (area under ROC >0.8) postoperative thresholds for tremor and rigidity improvements, as well as stimulation-induced motor contractions and paresthesias. The reliability was poor for improvement in bradykinesia., Conclusion: Intraoperative testing reliably predicts postoperative thresholds. These results are relevant during the informed consent process and patient counseling for DBS surgery. These will also guide the development of future methods for intraoperative feedback, especially during asleep DBS., (© 2019 International Neuromodulation Society.)

Objectives: Conventional targeting methods for neuromodulation therapies are insufficient for visualizing targets along white matter pathways and localizing targets in patient-specific space. Diffusion tensor imaging (DTI) holds promise for enhancing neuromodulation targeting by allowing detailed visualization of white matter tracts and their connections on an individual level., Material and Methods: We review the literature on DTI and neuromodulation, focusing on clinical studies that have utilized DTI tractography for surgical neuromodulation planning. This primarily includes the growing number of studies on tractography-guided targeting in deep brain stimulation as well as magnetic resonance-guided focused ultrasound., Results: In this review, we discuss three main topics: 1) an overview of the basic principles of DTI, its metrics, and tractography, 2) the evolution and utility of DTI to better guide neuromodulation targets, and 3) the ability of DTI to investigate structural connectivity and brain networks, and how such a network perspective may be an integral part of identifying new or optimal neuromodulation targets., Conclusion: There is increasing evidence that DTI is superior to conventional targeting methods with respect to improving brain stimulation therapies. DTI has the ability to better define anatomical targets by allowing detailed visualization of white matter tracts and localizing targets based on individual anatomy. Network analyses can lead to the identification of new or optimal stimulation targets based on understanding how target regions are connected. The integration of DTI as part of routine MRI and surgical planning offers a more personalized approach to therapy and may be an important path for the future of neuromodulation., (© 2020 International Neuromodulation Society.)

Device titration is a major challenge when using deep brain stimulation (DBS) to treat behavioral disorders. Unlike in movement disorders, there is no reliable real-time clinical feedback for changes in complex behaviors resulting from DBS. Here, a female patient receiving DBS of the nucleus accumbens for the treatment of morbid obesity underwent cognitive testing via the flanker task alongside traditional methods of device titration. One set of stimulation parameters administered during titration resulted in acute cognitive improvement (p = 0.033) and increased frontal engagement as measured by electroencephalography (left anterior: p = 0.007, right anterior: p = 0.005) relative to DBS-OFF. The same parameters resulted in the most weight-loss during long-term continuous stimulation (47.8 lbs lost in 129 days) compared to the results of other stimulation settings. Diffusion tensor imaging analyses showed increased connectivity to dorsal attention networks and decreased connectivity to the default mode network for optimal parameters (p < 0.01). Our results provide evidence that targeted cognitive testing is a potentially useful tool for capturing acute effects of DBS stimulation during titration and predicting long-term treatment outcomes., Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT01512134., (Copyright © 2020 Weichart, Sederberg, Sammartino, Krishna, Corrigan and Rezai.)

Background: The selection of optimal deep brain stimulation (DBS) parameters is time-consuming, experience-dependent, and best suited when acute effects of stimulation can be observed (e.g., tremor reduction)., Objectives: To test the hypothesis that optimal stimulation location can be estimated based on the cortical connections of DBS contacts., Methods: We analyzed a cohort of 38 patients with Parkinson's disease (24 training, and 14 test cohort). Using whole-brain probabilistic tractography, we first mapped the cortical regions associated with stimulation-induced efficacy (rigidity, bradykinesia, and tremor improvement) and side effects (paresthesia, motor contractions, and visual disturbances). We then trained a support vector machine classifier to categorize DBS contacts into efficacious, defined by a therapeutic window ≥2 V (threshold for side effect minus threshold for efficacy), based on their connections with cortical regions associated with efficacy versus side effects. The connectivity-based classifications were then compared with actual stimulation contacts using receiver-operating characteristics (ROC) curves., Results: Unique cortical clusters were associated with stimulation-induced efficacy and side effects. In the training dataset, 42 of the 47 stimulation contacts were accurately classified as efficacious, with a therapeutic window of ≥3 V in 31 (66%) and between 2 and 2.9 V in 11 (24%) electrodes. This connectivity-based estimation was successfully replicated in the test cohort with similar accuracy (area under ROC = 0.83)., Conclusions: Cortical connections can predict the efficacy of DBS contacts and potentially facilitate DBS programming. The clinical utility of this paradigm in optimizing DBS outcomes should be prospectively tested, especially for directional electrodes., (© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.)

Background: Disturbances in the reward network of the brain underlie addiction, depression, and obsessive-compulsive disorder. The ventral capsule/ventral striatum and nucleus accumbens (NAc) region is a clinically approved target for deep brain stimulation for obsessive-compulsive disorder., Methods: We performed a comprehensive literature review to define clinically relevant anatomy and connectivity of the ventral capsule/ventral striatum and NAc region to guide target selection for deep brain stimulation., Results: Architecturally and functionally, the NAc is divided into the core and the shell, with each area having different connections. The shell primarily receives limbic information, and the core typically receives information from the motor system. In general, afferents from the prefrontal cortex, hippocampus, and amygdala are excitatory. The dopaminergic projections to the NAc from the ventral tegmental area modulate the balance of these excitatory inputs. Several important inputs to the NAc converge at the junction of the internal capsule (IC) and the anterior commissure (AC): the ventral amygdalofugal pathways that run parallel to and underneath the AC, the precommissural fornical fibers that run anterior to the AC, axons from the ventral prefrontal cortex and medial orbitofrontal cortex that occupy the most ventral part of the IC and embedding within the NAc and AC, and the superolateral branch of the medial forebrain bundle located parallel to the anterior thalamic radiation in the IC., Conclusions: The caudal part of the NAc passing through the IC-AC junction may be an effective target for deep brain stimulation to improve behavioral symptoms associated with obsessive-compulsive disorder., (Copyright © 2019. Published by Elsevier Inc.)

Transcranial focused ultrasound (FUS) ablation is an emerging incision-less treatment for neurological disorders. The factors affecting FUS treatment efficiency are not well understood. Kranion is open-source software that allows the user to simulate the planning stages of FUS treatment and to "replay" previous treatments for off-line analysis. This study aimed to investigate the relationship between skull parameters and treatment efficiency and to create a metric to estimate temperature rise during FUS. CT images from 28 patients were analyzed to validate the use of Kranion. For stereotactic targets within each patient, individual transducer element incident angles, skull density ratio, and skull thickness measurements were recorded. A penetration metric (the "beam index") was calculated by combining the energy loss from incident angles and the skull thickness. Kranion accurately estimated the patient's skull and treatment parameters. The authors observed significant changes in incident angles with different targets in the brain. Using the beam index as a predictor of temperature rise in a linear-mixed-effects model, they were able to predict the average temperature rise at the focal point during ablation with < 21% error (55°C ± 3.8°C) in 75% of sonications, and with < 44% (55°C ± 7.9°C) in 97% of sonications. This research suggests that the beam index can improve the prediction of temperature rise during FUS. Additional work is required to study the relationship between temperature rise and lesion shape and clinical outcomes.

Objective: Physicians are more frequently encountering patients who are treated with deep brain stimulation (DBS), yet many MRI centers do not routinely perform MRI in this population. This warrants a safety assessment to improve DBS patients' accessibility to MRI, thereby improving their care while simultaneously providing a new tool for neuromodulation research., Methods: A phantom simulating a patient with a DBS neuromodulation device (DBS lead model 3387 and IPG Activa PC model 37601) was constructed and used. Temperature changes at the most ventral DBS electrode contacts, implantable pulse generator (IPG) voltages, specific absorption rate (SAR), and B1+rms were recorded during 3-T MRI scanning. Safety data were acquired with a transmit body multi-array receive and quadrature transmit-receive head coil during various pulse sequences, using numerous DBS configurations from "the worst" to "the most common."In addition, 3-T MRI scanning (T1 and fMRI) was performed on 41 patients with fully internalized and active DBS using a quadrature transmit-receive head coil. MR images, neurological examination findings, and stability of the IPG impedances were assessed., Results: In the phantom study, temperature rises at the DBS electrodes were less than 2°C for both coils during 3D SPGR, EPI, DTI, and SWI. Sequences with intense radiofrequency pulses such as T2-weighted sequences may cause higher heating (due to their higher SAR). The IPG did not power off and kept a constant firing rate, and its average voltage output was unchanged. The 41 DBS patients underwent 3-T MRI with no adverse event., Conclusions: Under the experimental conditions used in this study, 3-T MRI scanning of DBS patients with selected pulse sequences appears to be safe. Generally, T2-weighted sequences (using routine protocols) should be avoided in DBS patients. Complementary 3-T MRI phantom safety data suggest that imaging conditions that are less restrictive than those used in the patients in this study, such as using transmit body multi-array receive coils, may also be safe. Given the interplay between the implanted DBS neuromodulation device and the MRI system, these findings are specific to the experimental conditions in this study.

Background: Focused ultrasound thalamotomy (FUS-T) was recently approved for the treatment of refractory essential tremor (ET). Despite its noninvasive approach, FUS-T reinitiated concerns about the adverse effects and long-term efficacy after lesioning., Objective: To prospectively assess the outcomes of FUS-T in 10 ET patients using tractography-based targeting of the ventral intermediate nucleus (VIM)., Methods: VIM was identified at the intercommissural plane based on its neighboring tracts: the pyramidal tract and medial lemniscus. FUS-T was performed at the center of tractography-defined VIM. Tremor outcomes, at baseline and 3 mo, were assessed independently by the Tremor Research Group. We analyzed targeting coordinates, clinical outcomes, and adverse events. The FUS-T lesion location was analyzed in relation to unbiased thalamic parcellation using probabilisitic tractography. Quantitative diffusion-weighted imaging changes were also studied in fiber tracts of interest., Results: The tractography coordinates were more anterior than the standard. Intraoperatively, therapeutic sonications at the tractography target improved tremor (>50% improvement) without motor or sensory side effects. Sustained improvement in tremor was observed at 3 mo (tremor score: 18.3 ± 6.9 vs 8.1 ± 4.4, P = .001). No motor weakness and sensory deficits after FUS-T were observed during 6-mo follow-up. Ataxia was observed in 3 patients. FUS-T lesions overlapped with the VIM parcellated with probablisitic tractography. Significant microstructural changes were observed in the white matter connecting VIM with cerebellum and motor cortex., Conclusion: This is the first report of prospective VIM targeting with tractography for FUS-T. These results suggest that tractography-guided targeting is safe and has satisfactory short-term clinical outcomes.

Objective: Focused ultrasound thalamotomy is an emerging treatment for essential tremor, and it is ideal for studying reorganization in the human brain after acute injury because it creates a controlled thalamic ablation without breaching the cortex. However, there is not yet a metric capable of detecting microstructural changes in the presence of acute phase edema with good sensitivity in the chronic phase, when the lesion boundaries become inconspicuous., Methods: We prospectively studied microstructural changes at the lesion site using generalized q-sampling imaging with restricted diffusion imaging. We obtained diffusion-weighted MRI scans preoperatively, 1 day after (n = 18), and 1 year after (n = 9) focused ultrasound thalamotomy. The restricted diffusion imaging maps were compared at the group level, controlling for improvement in contralateral hand tremor., Results: The restricted diffusion imaging metric significantly increased in the 1 day post images, and the area with restricted diffusivity extended beyond the lesion boundaries identified on T2-weighted imaging. Two distinct zones of microstructural changes were identified, and the lesion area was identifiable at 1 year. The anterior and medial aspects of the lesion had a significant changes in RDI at 1 year, potentially signifying reorganization. The voxels with significant changes in restricted diffusion imaging values extend beyond the VIM into the surrounding white matter., Interpretation: Correcting for free water contamination with restricted diffusion imaging allowed us to study microstructural changes after focused ultrasound thalamotomy. We observed statistically significant changes in RDI in the anterior and medial aspect of the lesion at 1 year. Whether these changes represent tissue reorganization remains to be confirmed in future studies. These findings may support performing additional ablations antero-medially for durable efficacy., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To correlate the accumulated thermal dose (ATD) with lesion size in magnetic resonance (MR)-guided focused ultrasound (MRgFUS) thalamotomy to help guide future clinical treatments., Materials and Methods: Thirty-six patients with medication-refractory essential tremor were treated using a commercial MRgFUS brain system (ExAblate 4000, InSightec) in a 3T MR scanner (MR750, GE Healthcare). Intraoperative MR-thermometry was performed to measure the induced temperature and thermal dose distributions (thermal coefficient = -0.00909 ppm/°C). The ATD was calculated over multiple sonications with appropriate corrections for spatial-shifting artifacts. The ATD profile sizes obtained for dose values of 17, 40, 100, 200, and 240 cumulative equivalent minutes at 43°C (CEM) were correlated with the corresponding lesion sizes measured via axial T1- and T2-weighted MR images acquired 1 day post-treatment., Results: Of a total of 232 included sonications, 83 required corrections for off-resonance-induced spatial-shifting artifacts (correction range = [1.1,2.2] mm). The mean lesion sizes measured on T2-weighted MR images (6.2 ± 1.3 mm, mean ± SD) were 15% larger than those measured on corresponding T1-weighted MR images (5.3 ± 1.2 mm, mean ± SD). The ATD values that provided the best correlations with the measured lesion sizes on T2- and T1-weighted MR images were 100 and 200 CEM, respectively., Conclusion: The ATD was correlated with lesion size measured 1 day following MRgFUS thalamotomy for essential tremor. These data provide useful information for predicting brain lesion size and determining treatment endpoints in future clinical MRgFUS procedures., (© 2018 American Association of Physicists in Medicine.)

Life requires monitoring and adjusting behavior in the face of conflicts. The conflict monitoring theory implicates the anterior cingulate cortex (ACC) in these processes; its ventral aspect (vACC) specializes in emotional conflict. To elucidate the underpinning neural mechanism, we recorded vACC extracellular activity from 12 patients with mood disorders or epilepsy who performed the face-emotional Stroop task. Behaviorally, both conflict detection and adaptation to conflict were evident. The firing rate of neurons in the vACC represented current conflict, i.e., current-congruency. The late onset of the effect is compatible with a role in monitoring. Additionally, early responses of some neurons represented the immediate history of conflicts, i.e., previous-trial-congruency. Finally, in some neurons the response to the current-trial was modulated by previous-trial-congruency, laying the ground for adjusting-to-conflicts. Our results uncover a single neuron level mechanism in the vACC that encodes and integrates past and present emotional conflicts, allowing humans to accommodate their responses accordingly., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Deep brain stimulation of the ventro-intermedius nucleus of the thalamus is an established treatment for tremor of differing etiologies but factors that may predict the short- and especially long-term outcome of surgery are still largely unknown., Methods: We retrospectively investigated the clinical, pharmacological, electrophysiological and anatomical features that might predict the initial response and preservation of benefit in all patients who underwent deep brain stimulation for tremor. Data were collected at the following time points: baseline (preoperative), one-year post-surgery, and most recent visit. Tremor severity was recorded using the Fahn-Tolosa-Marin Tremor Rating Scale and/or the Unified Parkinson's Disease Rating Scale., Results: A total of 52 patients were included in the final analysis: 31 with essential tremor, 15 with cerebellar tremor of different etiologies, and 6 with Parkinson's disease. Long-term success (mean follow-up duration 34.7 months, range 1.7-121.1 months) was reported in 63.5%. Predictors of long-term benefit were: underlying tremor etiology (best outcome in Parkinson's disease, worst outcome in cerebellar tremor); age at surgery (the older the better); baseline tremor severity (the greater the better); lack of response to benzodiazepines; a more anterior electrode placement and single-unit beta power (the greater the better)., Conclusions: Specific patients' features (including single unit beta activity) and electrode locations may predict the short- and long-term benefit of thalamic stimulation for tremor. Future prospective studies enrolling a much larger sample of patients are needed to substantiate the associations detected by this retrospective study., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Importance: Magnetic resonance imaging-guided focused ultrasound ablation has been approved for the treatment of refractory essential tremor and is being studied for other neurological indications, including dyskinesias and tremor in Parkinson disease, dystonia, neuropathic pain, obsessive-compulsive disorder, epilepsy, and brain tumors., Objective: To review the scientific foundations of FUS technology, existing neurological applications, and future advances., Evidence Review: PubMed was searched for the past 10 years using the terms "transcranial ultrasound," "focused ultrasound," and "neurological applications." Relevant references were selected from the author's reference collection. From the 2855 unique records, 243 publications were screened. After excluding abstracts detailing in vitro studies or non-neurological applications, 86 full texts were retrieved for qualitative review., Findings: Advances in the transducer design and electronic phase correction have allowed efficient focusing of ultrasounds for transcranial treatment. The mid-frequency (650 kHz) transducer can make small (4-6 mm in diameter) and precise (accuracy of <2 mm) brain lesions. The treatment monitoring is achieved via "live" anatomical thermography imaging and clinical feedback. The initial results from its clinical application in movement disorders are encouraging. Emerging applications in epilepsy and neurobehavioral and cognitive disorders are being explored. The low-frequency (220 kHz) transducer coupled with microbubbles can potentially enable targeted drug delivery for novel applications, such as Alzheimer disease and brain tumors. Finally, neuromodulation with subthreshold sonications may allow the interrogation of brain areas previously not accessible for electrical stimulation., Conclusions and Relevance: Transcranial focused ultrasound for both ablative and nonablative applications is noninvasive, making it suitable for selected patients who are not candidates for conventional surgical options. Future advancements in imaging and sonication algorithms will improve the safety and efficacy of this technology.

Since its introduction, diffusion tensor imaging (DTI) has become an important tool in neuroscience given its unprecedented ability to image brain white matter in vivo. The interest in understanding the mechanisms of action of Deep Brain Stimulation in different targets and indications, together with the constant drive towards the improvement in long-term clinical outcomes, has found a logical complement in the application of tractography in this field. Diffusion tensor imaging has been traditionally associated with an increased susceptibility to MRI artifacts, and expensive computational resources. Recent advances have however improved these restrictions, allowing for countless applications in Neurosurgery, as demonstrated by the large number of original research papers published in the last decade. In this chapter, we review the current status of the implementation of DTI during DBS of the basal ganglia, discussing the findings, potential challenges and the expected improvements in surgical outcomes deriving by the routine use of tractography in functional neurosurgery., (© 2018 S. Karger AG, Basel.)

Background: Stereotactic headframe-based imaging is often needed for target localization during surgery for insertion of deep brain stimulators. A major concern during this surgery is the need for emergency airway management while an awake or sedated patient is in the stereotactic headframe. The aim of our study was to determine the ease of emergency airway management with a stereotactic headframe in situ., Materials and Methods: We conducted an observational study using a mannequin. A Leksell stereotactic headframe was placed on a mannequin in the operating room and the frame was fixed to the operating room table. Anesthesia personnel were asked to insert a #4 laryngeal mask and then to intubate the mannequin, using both direct (DL) and video laryngoscopy (VL). In addition, participants were asked to perform the same airway techniques in the mannequin without the headframe. Data were analyzed for time taken for airway management using different devices with and without the headframe. In addition, we compared the time taken to secure the airway between different participant groups., Results: Thirty anesthesia personnel (7 residents, 12 fellows, and 11 consultants) participated in the study. With the headframe in situ, 97% of participants were able to insert a laryngeal mask on their first attempt; 93% and 97% of participants were able to intubate the mannequin using DL and VL respectively on their first attempt. Without the stereotactic headframe, all participants were able to insert the laryngeal mask and intubate on the first attempt. The average time taken to insert a laryngeal mask and intubate the mannequin using DL and VL with the headframe in situ was 39.3, 58.6, and 54.8 seconds, respectively., Conclusions: Our study showed that both laryngeal mask insertion and tracheal intubation can be performed with a stereotactic headframe in situ. A laryngeal mask is the quickest airway device to insert and can be inserted while the mannequin is in the standard surgical position. Further study is needed to validate the results in patients.

Background/aims: Interleaving stimulation (ILS) in deep brain stimulation (DBS) provides individualized stimulation of 2 contacts delivered in alternating order. Currently, limited information on the utility of ILS exists. The aims of this study were to determine the practical applications and outcomes of ILS DBS in Parkinson's disease (PD), tremor, and dystonia., Methods: We performed a single-center, unblinded, retrospective chart review of all patients with DBS attempted on ILS at our referral center assessing for rationale and outcomes., Results: Fifty patients (PD, n = 27; tremor, n = 7; dystonia, n = 16 patients) tried ILS for 2 rationales: management of adverse effects (n = 29) and to improve clinical efficacy (n = 21). A total of 19 patients demonstrated improvement with ILS for adverse effect management predominately for the treatment of dyskinesias (n = 12). In the vast majority of dyskinetic patients, a contact added into the rostral zona incerta with ILS was performed. Nine out of 21 patients demonstrated improved clinical efficacy with ILS with all 6 PD patients who tried ILS for this rationale demonstrating benefit., Conclusions: In PD, ILS provided benefits for dyskinesias and parkinsonism, with minimal improvement of other adverse effects. In tremor and dystonia, marginal effects in terms of mitigation of adverse effects and improvement of clinical outcomes were evident., (© 2019 S. Karger AG, Basel.)

Background: Thalamic deep brain stimulation (DBS) is an effective strategy for treatment of essential tremor (ET). With limitations of imaging modalities, targeting largely relies on indirect methods. This study was designed to determine the optimal target for DBS in ET and construct a targeting method based on probabilistic maps., Methods: Patients with ET who had sustained tremor reduction at 1 year and optimal microelectrode recordings were selected. Stimulation volume was individually modeled in standard space, and a final optimal region was derived for the whole population. A fornix (FX) targeting method was developed to determine the location of the optimal stimulation site relative to the FX and posterior commissure (PC) in the anteroposterior plane, the border between the thalamus and internal capsule in the mediolateral plane, and the anterior commissure (AC)-PC (AC-PC) plane in the dorsoventral axis. Following comparative analyses with other standard indirect methods (25% of AC-PC and PC + 6 mm), the FX method was studied in relation to diffusion tensor imaging., Results: Using the FX method, the optimal stimulation site was at the intersection of two thirds and one third of the PC-FX distance (mean of 28% ± 1.5 AC-PC length) and 4 mm medial to the lateral border of the thalamus. Compared with previously used methods, there was a significant reduction in variability of the optimal stimulation site with the FX method. The target defined using this strategy was found to be within the boundaries of the dentatorubrothalamic tract., Conclusions: The FX method may be an additional targeting strategy in patients undergoing thalamic DBS surgery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Diffusion-weighted imaging (DWI)-based tractography has gained increasing popularity as a method for detailed visualization of white matter (WM) tracts. Different imaging techniques, and more novel, advanced imaging methods provide significant WM structural detail. While there has been greater focus on improving tract visualization for larger WM pathways, the relative value of each method for cranial nerve reconstruction and how this methodology can assist surgical decision-making is still understudied. Images from 10 patients with posterior fossa tumors (4 male, mean age: 63.5), affecting either the trigeminal nerve (CN V) or the facial/vestibular complex (CN VII/VIII), were employed. Three distinct reconstruction methods [two tensor-based methods: single diffusion tensor tractography (SDT) (3D Slicer), eXtended streamline tractography (XST), and one fiber orientation distribution (FOD)-based method: streamline tractography using constrained spherical deconvolution (CSD)-derived estimates (MRtrix3)], were compared to determine which of these was best suited for use in a neurosurgical setting in terms of processing speed, anatomical accuracy, and accurate depiction of the relationship between the tumor and affected CN. Computation of the tensor map was faster when compared to the implementation of CSD to provide estimates of FOD. Both XST and CSD-based reconstruction methods tended to give more detailed representations of the projections of CN V and CN VII/VIII compared to SDT. These reconstruction methods were able to more accurately delineate the course of CN V and CN VII/VIII, differentiate CN V from the cerebellar peduncle, and delineate compression of CN VII/VIII in situations where SDT could not. However, CSD-based reconstruction methods tended to generate more invalid streamlines. XST offers the best combination of anatomical accuracy and speed of reconstruction of cranial nerves within this patient population. Given the possible anatomical limitations of single tensor models, supplementation with more advanced tensor-based reconstruction methods might be beneficial.

OBJECTIVE The aim of this study was to evaluate the safety of 3-T MRI in patients with implanted deep brain stimulation (DBS) systems. METHODS This study was performed in 2 phases. In an initial phantom study, a Lucite phantom filled with tissue-mimicking gel was assembled. The system was equipped with a single DBS electrode connected to an internal pulse generator. The tip of the electrode was coupled to a fiber optic thermometer with a temperature resolution of 0.1°C. Both anatomical (T1- and T2-weighted) and functional MRI sequences were tested. A temperature change within 2°C from baseline was considered safe. After findings from the phantom study suggested safety, 10 patients with implanted DBS systems targeting various brain areas provided informed consent and underwent 3-T MRI using the same imaging sequences. Detailed neurological evaluations and internal pulse generator interrogations were performed before and after imaging. RESULTS During phantom testing, the maximum temperature increase was registered using the T2-weighted sequence. The maximal temperature changes at the tip of the DBS electrode were < 1°C for all sequences tested. In all patients, adequate images were obtained with structural imaging, although a significant artifact from lead connectors interfered with functional imaging quality. No heating, warmth, or adverse neurological effects were observed. CONCLUSIONS To the authors' knowledge, this was the first study to assess the clinical safety of 3-T MRI in patients with a fully implanted DBS system (electrodes, extensions, and pulse generator). It provided preliminary data that will allow further examination and assessment of the safety of 3-T imaging studies in patients with implanted DBS systems. The authors cannot advocate widespread use of this type of imaging in patients with DBS implants until more safety data are obtained.

OBJECTIVE The authors explored the feasibility of seizure detection and prediction using signals recorded from the anterior thalamic nucleus, a major target for deep brain stimulation (DBS) in the treatment of epilepsy. METHODS Using data from 5 patients (13 seizures in total), the authors performed a feasibility study and analyzed the performance of a seizure prediction and detection algorithm applied to simultaneously acquired scalp and thalamic electroencephalography (EEG). The thalamic signal was obtained from DBS electrodes. The applied algorithm used the similarity index as a nonlinear measure for seizure identification, with patient-specific channel and threshold selection. Receiver operating characteristic (ROC) curves were calculated using data from all patients and channels to compare the performance between DBS and EEG recordings. RESULTS Thalamic DBS recordings were associated with a mean prediction rate of 84%, detection rate of 97%, and false-alarm rate of 0.79/hr. In comparison, scalp EEG recordings were associated with a mean prediction rate of 71%, detection rate of 100%, and false-alarm rate of 1.01/hr. From the ROC curves, when considering all channels, DBS outperformed EEG for both detection and prediction of seizures. CONCLUSIONS This is the first study to compare automated seizure detection and prediction from simultaneous thalamic and scalp EEG recordings. The authors have demonstrated that signals recorded from DBS leads are more robust than EEG recordings and can be used to predict and detect seizures. These results indicate feasibility for future designs of closed-loop anterior nucleus DBS systems for the treatment of epilepsy.

OBJECTIVE The ventral intermediate nucleus (VIM) of the thalamus is not visible on structural MRI. Therefore, direct VIM targeting methods for stereotactic tremor surgery are desirable. The authors previously described a direct targeting method for visualizing the VIM and its structural connectivity using deterministic tractography. In this combined electrophysiology and imaging study, the authors investigated the electrophysiology within this tractography-defined VIM (T-VIM). METHODS Thalamic neurons were classified based on their relative location to the T-VIM: dorsal, within, and ventral to the T-VIM. The authors identified the movement-responsive cells (kinesthetic and tremor cells), performed spike analysis (firing rate and burst index), and local field potential analysis (area under the curve for 13-30 Hz). Tremor efficacy in response to microstimulation along the electrode trajectory was also assessed in relation to the T-VIM. RESULTS Seventy-three cells from a total of 9 microelectrode tracks were included for this analysis. Movement-responsive cells (20 kinesthetic cells and 26 tremor cells) were identified throughout the electrode trajectories. The mean firing rate and burst index of cells (n = 27) within the T-VIM are 18.8 ± 9.8 Hz and 4.5 ± 5.4, respectively. Significant local field potential beta power was identified within the T-VIM (area under the curve for 13-30 Hz = 6.6 ± 7.7) with a trend toward higher beta power in the dorsal T-VIM. The most significant reduction in tremor was also observed in the dorsal T-VIM. CONCLUSIONS The electrophysiological findings within the VIM thalamus defined by tractography, or T-VIM, correspond with the known microelectrode recording characteristics of the VIM in patients with tremor.

Background: Stuttering is a speech disorder with disruption of verbal fluency, occasionally present in Parkinson's disease (PD). PD co-incident stuttering may either worsen or improve after Deep Brain Stimulation (DBS)., Methods: Sixteen out of 453 PD patients (3.5%) exhibited stuttering after DBS (PD-S) and were compared with a group of patients without stuttering (PD-NS) using non-parametric statistics., Results: After DBS, stuttering worsened in 3 out of 4 patients with co-incidental stuttering. Most PD-S underwent subthalamic (STN) DBS, but 4 were implanted in the globus pallidus (GPi). Nine out of 16 PD-S (56.3%) reported a positive familial history for stuttering compared to none of the PD-NS. PD-S were mainly male (81.3%) with slight worse motor features compared to PD-NS., Conclusion: Herein, we describe a group of PD patients developing stuttering after DBS and report the presence of a positive familial history for stuttering as the most relevant risk factor, suggesting a possible underlying genetic cause. The fact that stuttering occurred after either STN or GPi DBS is an argument against the impact of medication reduction on stuttering., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Movement disorder surgery has evolved throughout history as our knowledge of motor circuits and ways in which to manipulate them have expanded. Today, the positive impact on patient quality of life for a growing number of movement disorders such as Parkinson's disease is now well accepted and confirmed through several decades of randomized, controlled trials. Nevertheless, residual motor symptoms after movement disorder surgery such as deep brain stimulation and lack of a definitive cure for these conditions demand that advances continue to push the boundaries of the field and maximize its therapeutic potential. Similarly, advances in related fields - wireless technology, artificial intelligence, stem cell and gene therapy, neuroimaging, nanoscience, and minimally invasive surgery - mean that movement disorder surgery stands at a crossroads to benefit from unique combinations of all these developments. In this minireview, we outline some of these developments as well as evidence supporting topics of recent discussion and controversy in our field. Moving forward, expectations remain high that these improvements will come to encompass an even broader range of patients who might benefit from this therapy and decrease the burden of disease associated with these conditions. © 2016 International Parkinson and Movement Disorder Society., (© 2016 International Parkinson and Movement Disorder Society.)

OBJECTIVE The diagnosis of Chiari malformation Type I (CM-I) is primarily based on the degree of cerebellar tonsillar herniation even though it does not always correlate with symptoms. Neurological dysfunction in CM-I presumably results from brainstem compression. With the premise that conventional MRI does not reveal brain microstructural changes, this study examined both structural and microstructural neuroimaging metrics to distinguish patients with CM-I from age- and sex-matched healthy control subjects. METHODS Eight patients with CM-I and 16 controls were analyzed. Image postprocessing involved coregistration of anatomical T1-weighted with diffusion tensor images using 3D Slicer software. The structural parameters included volumes of the posterior fossa, fourth ventricle, and tentorial angle. Fractional anisotropy (FA) was calculated separately in the anterior and posterior compartments of the lower brainstem. RESULTS The mean age of patients in the CM-I cohort was 42.6 ± 10.4 years with mean tonsillar herniation of 12 mm (SD 0.7 mm). There were no significant differences in the posterior fossa volume (p = 0.06) or fourth ventricular volume between the 2 groups (p = 0.11). However, the FA in the anterior brainstem compartment was significantly higher in patients with CM-I preoperatively (p = 0.001). The FA values normalized after Chiari decompression except for persistently elevated FA in the posterior brainstem compartment in patients with CM-I and syrinx. CONCLUSIONS In this case-control study, microstructural alterations appear to be reliably associated with the diagnosis of CM-I, with a significantly elevated FA in the lower brainstem in patients with CM-I compared with controls. More importantly, the FA values normalized after decompressive surgery. These findings should be validated in future studies to determine the significance of diffusion tensor imaging-based assessment of brainstem microstructural integrity as an adjunct to the clinical assessment in patients with CM-I.

Background: Parkinson's disease patients undergoing subthalamic nucleus deep brain stimulation (STN DBS) at standard frequency (>100 Hz) often develop gait impairment, postural instability and speech difficulties. Low frequency stimulation (<100 Hz, LFS) can improve such axial symptoms, but there are concerns that improvement may be transient., Objective: To identify long-term outcome and predictors of low-frequency subthalamic stimulation in Parkinson's disease., Methods: Through a chart review we identified 85 out of 324 STN DBS patients who received a trial of LFS and describe their characteristics and outcome predictors., Results: Patients were switched to LFS (<100 Hz) 3.8 ± 3.3 years after surgery. Most patients (64%) attained a subjective improvement of gait, speech or balance for 2.0 ± 1.9 years. Motor scores improved within the first year after the stimulation change and showed a slower progression over time when compared to patients switched back to high frequency stimulation. UPDRS III axial score on medication before surgery and the y-axis coordinate of the active contact were independent predictors of LFS retention., Conclusions: This report provides evidence that the use of LFS yields an enduring benefit in a considerable percentage of patients who develop axial motor symptoms during conventional stimulation., (Copyright © 2016 Elsevier Inc. All rights reserved.)