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Patients with advanced Parkinson's disease often suffer from severe gait and balance problems, impacting quality of live and persisting despite optimization of standard therapies. The aim of this review was to systematically review the efficacy of STN-DBS programming techniques in alleviating gait disturbances in patients with advanced PD. Searches were conducted in PubMed, Embase, and Lilacs databases, covering studies published until May 2024. The review identified 36 articles that explored five distinct STN-DBS techniques aimed at addressing gait and postural instability in Parkinson's patients: low-frequency stimulation, ventral STN stimulation for simultaneous substantia nigra activation, interleaving, asymmetric stimulation and a short pulse width study. Among these, 21 articles were included in the meta-analysis, which revealed significant heterogeneity among studies. Notably, low-frequency STN-DBS demonstrated positive outcomes in total UPDRS-III score and FOG-Q, especially when combined with dopaminergic therapy. The most favorable results were found for low-frequency STN stimulation. The descriptive analysis suggests that unconventional stimulation approaches may be viable for gait problems in patients who do not respond to standard therapies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The amygdala consists of a collection of nuclei that are deep within the medial temporal lobe. Despite its small size, the amygdala is one of the most densely connected structures in the brain, and it plays a role in many superior neural functions, including neurovegetative control, motor control, memory processing, and neuromodulation. Advances in neuroimaging technology for examining brain activity have opened up new ways of understanding the functional contribution of this structure to emotions, learning, and related memories. Many studies have shown that the amygdala plays a key role in the pathophysiology of neuropsychiatric disorders, such as anxiety disorders, depression, aggression, and temporal epilepsy. This article reviews the anatomical structure of the amygdaloid complex and the connectivity among its subdivisions and with other brain structures, which will serve as a basis for understanding the clinical correlations., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: We are in the process of designing and testing an intradural stimulation device that will shorten the distance between the location of the electrode array and the targeted neural tissue, thus improving the efficacy of electrical current delivery. Identifying a biomarker that accurately reflects the response to this intervention is highly valued because of the potential to optimize interventional parameters or predict a response before it is clinically measurable. In this report, we summarize the findings pertaining to the study of biomarkers so that we and others will have an up-to-date reference that critically evaluates the current approaches and select one or several for testing during the development of our device., Materials and Methods: We have conducted a broad survey of the existing literature to catalogue the biomarkers that could be coupled to intradural spinal cord stimulation. We describe in detail some of the most promising biomarkers, existing limitations, and suitability to managing chronic pain., Results: Chronic, intractable pain is an all-encompassing condition that is incurable. Many treatments for managing chronic pain are nonspecific in action and intermittently administered; therefore, patients are particularly susceptible to large fluctuations in pain control over the course of a day. The absence of a reliable biomarker challenges assessment of therapeutic efficacy and contributes to either incomplete and inconsistent pain relief or, alternatively, intolerable side effects. Fluctuations in metabolites or inflammatory markers, signals captured during dynamic imaging, and genomics will likely have a role in governing how a device is modulated., Conclusions: Efforts to identify one or more biomarkers are well underway with some preliminary evidence supporting their efficacy. This has far-reaching implications, including improved outcomes, fewer adverse events, harmonization of treatment and individuals, performance gains, and cost savings. We anticipate that novel biomarkers will be used widely to manage chronic pain., (© 2020 International Neuromodulation Society.)

Objective: Deep brain stimulation (DBS) is an effective therapy for different neurological diseases, despite the lack of comprehension of its mechanism of action. The use of nonhuman primates (NHPs) has been historically important in advancing this field and presents a unique opportunity to uncover the therapeutic mechanisms of DBS, opening the way for optimization of current applications and the development of new ones. To be informative, research using NHPs should make use of appropriate electrode implantation tools. In the present work, the authors report on the feasibility and accuracy of targeting different deep brain regions in NHPs using a commercially available frameless stereotactic system (microTargeting platform)., Methods: Seven NHPs were implanted with DBS electrodes, either in the subthalamic nucleus or in the cerebellar dentate nucleus. A microTargeting platform was designed for each animal and used to guide implantation of the electrode. Imaging studies were acquired preoperatively for each animal, and were subsequently analyzed by two independent evaluators to estimate the electrode placement error (EPE). The interobserver variability was assessed as well., Results: The radial and vector components of the EPE were estimated separately. The magnitude of the vector of EPE was 1.29 ± 0.41 mm and the mean radial EPE was 0.96 ± 0.63 mm. The interobserver variability was considered negligible., Conclusions: These results reveal the suitability of this commercial system to enhance the surgical insertion of DBS leads in the primate brain, in comparison to rigid traditional frames. Furthermore, our results open up the possibility of performing frameless stereotaxy in primates without the necessity of relying on expensive methods based on intraoperative imaging.

Introduction : Translating basic science research into a safe and effective therapy for spinal cord injury (SCI) requires suitable large animal models for testing both implantable devices and biologic approaches to better approximate human anatomy and function. Hemisection lesions, routinely used for investigational purposes in small animals, are less frequently described in large animals that might be appropriate for translational studies. Size constraints of small animals (mice and rats) limits the predictability of the findings when scaled up. Our goal is to review the status of hemisection SCI in large animals across species and time to prepare for the testing of a novel intradural spinal cord stimulation device for control of spasticity in an ovine model. Methods and Results : We surveyed the literature on hemisection in quadrupeds and nonhuman primates, and catalogued the species, protocols and outcomes of the experimental work in this field. Feline, lapine, canine, simian, porcine, ovine and bovine models were the primary focal points. There is a consistent body of literature reporting use of the hemisection approach in large animals, but with differences in surgical technique depending on the goals and nature of the individual studies. While the injuries are not always consistent, the experimental variability is generally lower than that of the contusion-based approach. In general, as the body size of the animal increases, animal care requirements and the associated costs follow. In most cases, this is inversely correlated with the number of animals used in hemisection models. Conclusions : The hemisection approach to modeling SCI is straightforward compared with other methods such as the contusive impact and enables the transection of isolated ascending and descending tracts and segment specific cell bodies. This has certain advantages in models investigating post-injury axonal regrowth. However, this approach is not generally in line with the patho-physiologies encountered in SCI patients. Even so, the ability to achieve more control over the level of injury makes it a useful adjunct to contusive and ischemic approaches, and suggests a useful role in future translational studies.

Objective: Parkinson's disease (PD) is a progressive neurological movement disorder that is commonly treated with deep brain stimulation (DBS) surgery in advanced stages. The purpose of this study was to investigate factors that affect time to placement of a second-sided DBS lead for PD when a unilateral lead is initially placed for asymmetrical presentation. The decision whether to initially perform unilateral or bilateral DBS is largely based on physician and/or patient preference., Methods: This study was a retrospective cohort analysis of patients with PD undergoing initial unilateral DBS for asymmetrical disease between January 1999 and December 2017 at the authors' institution. Patients treated with DBS for essential tremor or other conditions were excluded. Variables collected included demographics at surgery, time since diagnosis, Unified Parkinson's Disease Rating Scale motor scores (UPDRS-III), patient-reported quality-of-life outcomes, side of operation, DBS target, intraoperative complications, and date of follow-up. Paired t-tests were used to assess mean changes in UPDRS-III. Cox proportional hazards analysis and the Kaplan-Meier method were used to determine factors associated with time to second lead insertion over 5 years., Results: The final cohort included 105 patients who underwent initial unilateral DBS for asymmetrical PD; 59% of patients had a second-sided lead placed within 5 years with a median time of 34 months. Factors found to be significantly associated with early second-sided DBS included patient age 65 years or younger, globus pallidus internus (GPi) target, and greater off-medication reduction in UPDRS-III score following initial surgery. Older age was also found to be associated with a smaller preoperative UPDRS-III levodopa responsiveness score and with a smaller preoperative to postoperative medication-off UPDRS-III change., Conclusions: Younger patients, those undergoing GPi-targeted unilateral DBS, and patients who responded better to the initial DBS were more likely to undergo early second-sided lead placement. Therefore, these patients, and patients who are more responsive to medication preoperatively (as a proxy for DBS responsiveness), may benefit from consideration of initial bilateral DBS.

Introduction: Deep brain stimulation (DBS) is a widely accepted therapy for Parkinson's disease. While outcome predictors such as levodopa-response are well established, there remains a need for objective and unbiased predictors in clinical practice. We performed an exploratory study to examine whether cortical thickness, derived from preoperative MRI, correlates with postoperative outcome., Methods: Using freesurfer, we retrospectively measured cortical thickness on the preoperative MRI of 38 patients who underwent bilateral STN-DBS for PD during a 4-year period. The Unified Parkinson Disease Rating motor (UPDRS III) and experiences of daily living subscales (UPDRS II) were collected at baseline and six months after surgery. As an initial analysis, a series of partial correlations was conducted to evaluate the association between postoperative outcome scores and average cortical thickness from predefined regions of interest, adjusting for candidate confounders, without correcting for multiple comparisons. A confirmatory vertex-wise analysis was performed using a cluster-wise correction for multiple comparisons., Results: Based on the ROI analysis, the strongest correlation with motor outcome was found to be with the left lateral-occipital cortex. Patients with greater cortical thickness in this area presented with greater improvements in motor scores. This relationship was also supported by the vertex-wise analysis. Greater cortical thickness in frontal and temporal regions may be correlated with greater post-operative improvements in UPDRS II, but this was not confirmed in the vertex-wise analysis., Conclusions: Our data indicate that greater cortical thickness in visuo-motor areas is correlated with motor outcomes after DBS for PD. Further prospective investigations are needed to confirm our findings and better-investigate potential image biomarkers., Competing Interests: Declaration of competing interest Andre G. Machado: Consulting fees from St. Jude and has distribution rights from Enspire, ATI, and Cardionomics. The other authors have no disclosures relevant to this study., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Deep brain stimulation (DBS) has been considered for patients with intractable pain syndromes since the 1950s. Although there is substantial experience reported in the literature, the indications are contested, especially in the United States where it remains off-label. Historically, the sensory-discriminative pain pathways were targeted. More recently, modulation of the affective sphere of pain has emerged as a plausible alternative., Objective: To systematically review the literature from studies that used contemporary DBS technology. Our aim is to summarize the current evidence of this therapy., Methods: A systematic search was conducted in the MEDLINE, EMBASE, and Cochrane libraries through July 2017 to review all studies using the current DBS technology primarily for pain treatment. Study characteristics including patient demographics, surgical technique, outcomes, and complications were collected., Results: Twenty-two articles were included in this review. In total, 228 patients were implanted with a definitive DBS system for pain. The most common targets used were periaqueductal/periventricular gray matter region, ventral posterior lateral/posterior medial thalamus, or both. Poststroke pain, phantom limb pain, and brachial plexus injury were the most common specific indications for DBS. Outcomes varied between studies and across chronic pain diagnoses. Two different groups of investigators targeting the affective sphere of pain have demonstrated improvements in quality of life measures without significant reductions in pain scores., Conclusion: DBS outcomes for chronic pain are heterogeneous thus far. Future studies may focus on specific pain diagnosis rather than multiple syndromes and consider randomized placebo-controlled designs. DBS targeting the affective sphere of pain seems promising and deserves further investigation., (Copyright © 2019 by the Congress of Neurological Surgeons.)

Introduction: We are developing a novel intradural spinal cord stimulator for treatment of neuropathic pain and spasticity. A key feature is the means by which it seals the dura mater to prevent leakage of cerebrospinal fluid (CSF). We have built and employed a test rig that enables evaluation of candidate seal materials., Methods: To guide the design of the test rig, we reviewed the literature on neurosurgical durotomies. The test rig has a mock durotomy slot with a dural substitute serving as the surrogate dura mater and water as the CSF. The primary experimental goal was to evaluate the effectiveness of candidate gasket materials as seals against CSF leakage in an implanted prototype device, at both normal and super-physiologic pressures. A secondary goal was to measure the transmembrane flows in a representative dural substitute material, to establish its baseline aqueous transport properties., Results: The seals prevented leakage of water at the implantation site over periods of ≈ ten days, long enough for the scar tissue to form in the clinical situation. The seals also held at water pressure transients approaching 250 mm Hg. The residual volumetric flux of water through the dura substitute membrane (Durepair®) was δV T /A ≈ 0.24 mm 3 /min/cm 2 , consistent with expectations for transport through the porous membrane prior to closure and equalization of internal/external pressures., Conclusions: We have demonstrated the workability of obtaining robust seal against leakage at the implantation site of a novel intradural stimulator using a custom-designed test rig. Extension of the method to in vivo testing in a large animal model will be the next step., (© 2019 International Neuromodulation Society.)

Background: There is a growing attention to determine the factors that predict quality of life (QoL) improvement after deep brain stimulation (DBS) for Parkinson's disease. Prior literature has largely focused on examining predictors one at a time, sometimes controlling for covariates., Objective: To develop a model that could be used as a nomogram to predict improvement in QoL following DBS surgery in patients with Parkinson's disease., Methods: All patients with complete pre- and postoperative movement disorder and neuropsychological testing who underwent DBS at a single institution between 2007-2012 were analyzed. The Parkinson's Disease Questionnaire-39 (PDQ-39) was used to measure QoL. Potential predictive factors, including patient demographics, clinical presentation characteristics, radiographic imaging, and motor and psychological testing were analyzed for impact on QoL., Results: Sixty-seven patients were identified, 36 (53.73%) of whom had meaningfully improved QoL following surgery. Five baseline variables showed significant relationships with the outcome: years since symptom onset, percent change in on/off motor evaluation, levodopa equivalent daily dose, bilateral vs unilateral DBS implantation, and PDQ-39 score. The final model includes PDQ-39, percent change in UPRS-III, and years since symptom onset and is able to predict improvement in QoL with 81% accuracy., Conclusion: Our model accurately predicted whether QoL would improve in patients undergoing subthalamic nucleus DBS 81% of the time. Our data may serve as the foundation to further refine a clinically relevant prognostic tool that would assist the decision-making process for clinicians and DBS multidisciplinary teams assessing patient candidacy for surgery., (Copyright © 2018 by the Congress of Neurological Surgeons.)

Objective: Spinal cord stimulation (SCS) is both relatively safe and reversible. Although SCS is generally regarded as a last resort, some of these patients will undergo additional spinal surgery after the device has been implanted or after its removal. We present a descriptive study of subsequent spinal surgery after SCS implantation., Methods: A retrospective review of patients who had undergone percutaneous or paddle SCS lead placement at our institution from 2009 to 2016 was performed. Patients who had only undergone trials or who had not undergone spine surgery after SCS implantation were excluded., Results: We identified 22 patients (5.7%) who had undergone spine surgery during the course of SCS treatment or after SCS removal, or both, of a total 383 patients who had undergone paddle and/or percutaneous SCS implantation. The most common additional spine interventions included lumbosacral decompression and fusion (n = 15; 42%). Of 36 surgeries, the most frequent indications for subsequent intervention were stenosis or restenosis (n = 16; 73%) and spine deformity (n = 6; 27%). The median EuroQol-5D index was 0.397 preoperatively and 0.678 postoperatively., Conclusions: To the best of our knowledge, the present study is the first to describe spine surgery in the setting of SCS implantation. Our results have indicated that spine surgery subsequent to, or concurrent with, SCS implantation appears to occur in few patients. Our study results suggest a modest improvement in quality of life outcomes. Therefore, clinicians should remember that patients might require further spine surgery despite the use of SCS implantation and, thus, might require reevaluation by the spine team., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Providing durable long-term pain control for patients with complex regional pain syndrome (CRPS) is challenging. A multidisciplinary approach focused on physical therapy is frequently prescribed, with opioids and invasive procedures reserved for those challenged by functional progression. In this study, we examined the long-term efficacy of intrathecal drug delivery systems (IDDS) in patients with CRPS at our institution., Methods: Patients with CRPS implanted with an IDDS between 2000 and 2013 who had four or more years of continuous follow-up were included in the analysis. The outcome variables of interest were pain intensity and oral opioid intake. The primary predictor of interest was dose of intrathecal opioids, with ziconotide, bupivacaine, and clonidine characterized as binary secondary predictors., Results: Of the 1,653 IDDS identified, 62 were implanted primarily for CRPS-related pain. Of these, 26 had four or more years of complete follow-up data. Pain scores did not significantly decrease over time, and we observed no correlation between pain intensity and use of any intrathecal medication. Although oral opioid intake decreased over time, intrathecal opioid dose did not affect oral opioid consumption. Ziconotide was associated with a hastening of the decrease in oral opioid intake, whereas the presence of bupivacaine paradoxically increased oral opioid intake., Conclusions: Our study demonstrates that intrathecal opioid dose was not associated with long-term decreases in oral opioid intake. Additionally, ziconotide was associated with a decrease in oral opioid intake over the four-year follow-up, and bupivacaine was associated with an increase in oral opioid intake. Our study examines the long-term effectiveness of intrathecal medications in managing pain in patients with complex regional pain syndrome. We present a detailed follow-up over four years for 26 patients, tracking oral opiate intake, pain scores, and intrathecal pump settings. Our findings suggest that intrathecal opiates may not be effective in reducing oral opiate intake, ziconotide may hasten a decrease in intake, and bupivacaine may lead to an increase in intake., (© 2018 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

OBJECTIVEThe authors' aim in this study was to evaluate placement accuracy and clinical outcomes in patients who underwent implantation of deep brain stimulation devices with the aid of frame-based stereotaxy and intraoperative MRI after induction of general anesthesia.METHODSThirty-three patients with movement disorders (27 with Parkinson's disease) underwent implantation of unilateral or bilateral deep brain stimulation systems (64 leads total). All patients underwent the implantation procedure with standard frame-based techniques under general anesthesia and without microelectrode recording. MR images were acquired immediately after the procedure and fused to the preoperative plan to verify accuracy. To evaluate clinical outcome, different scales were used to assess quality of life (EQ-5D), activities of daily living (Unified Parkinson's Disease Rating Scale [UPDRS] part II), and motor function (UPDRS part III during off- and on-medication and off- and on-stimulation states). Accuracy was assessed by comparing the coordinates (x, y, and z) from the preoperative plan and coordinates from the tip of the lead on intraoperative MRI and postoperative CT scans.RESULTSThe EQ-5D score improved or remained stable in 71% of the patients. When in the off-medication/on-stimulation state, all patients reported significant improvement in UPDRS III score at the last follow-up (p < 0.001), with a reduction of 25.2 points (46.3%) (SD 14.7 points and 23.5%, respectively). There was improvement or stability in the UPDRS II scores for 68% of the Parkinson's patients. For 2 patients, the stereotactic error was deemed significant based on intraoperative MRI findings. In these patients, the lead was removed and replaced after correcting for the error during the same procedure. Postoperative lead revision was not necessary in any of the patients. Based on findings from the last intraoperative MRI study, the mean difference between the tip of the electrode and the planned target was 0.82 mm (SD 0.5 mm, p = 0.006) for the x-axis, 0.67 mm (SD 0.5 mm, p < 0.001) for the y-axis, and 0.78 mm (SD 0.7 mm, p = 0.008) for the z-axis. On average, the euclidian distance was 1.52 mm (SD 0.6 mm). In patients who underwent bilateral implantation, accuracy was further evaluated comparing the first implanted side and the second implanted side. There was a significant mediolateral (x-axis) difference (p = 0.02) in lead accuracy between the first (mean 1.02 mm, SD 0.57 mm) and the second (mean 0.66 mm, SD 0.50 mm) sides. However, no significant difference was found for the y- and z-axes (p = 0.10 and p = 0.89, respectively).CONCLUSIONSFrame-based DBS implantation under general anesthesia with intraoperative MRI verification of lead location is safe, accurate, precise, and effective compared with standard implantation performed using awake intraoperative physiology. More clinical trials are necessary to directly compare outcomes of each technique.

Introduction: Implanted intrathecal drug delivery systems (IDDS) are increasingly used in the treatment of spasticity and in patients with refractory pain. Literature discussing complications associated with intrathecal pump placement is widely available. However, reports of complications following the removal of chronically placed catheters are scarce. We reviewed our series of patients who had surgery to remove the intrathecal catheter., Methods: Retrospective review was performed for all patients who underwent surgery to remove a catheter linked to an IDDS between 2010 and 2016. Patients older than 18 years were included in final analysis. Demographic (including age at removal, sex, BMI, and comorbidities) and etiologic characteristics (indications of IDDS implant and explant, interval between implant and explant, and concomitant surgery) were analyzed. Simple logistic regression was performed to seek any potential predictor of complications., Results: Fifty-nine patients underwent removal of their intrathecal catheter after variable periods (mean interval of 189 months). On eight occasions, patients developed complications after catheter removal (mean interval between implant and explant was 76 months for these cases). Retained catheter was the cause of complications in half of these occasions. Persistent cerebrospinal fluid leak was the next most common complication, with requirement of an external ventricular drain and lumbar drain to facilitate wound healing on two separate occasions., Conclusion: Removal of an intrathecal catheter from IDDS systems may cause complications that in some cases require additional surgery., (© 2018 International Neuromodulation Society.)

Introduction: The intrathecal space remains underutilized for diagnostic testing, invasive monitoring or as a pipeline for the delivery of neurological therapeutic agents and devices. The latter including drug infusions, implants for electrical modulation, and a means for maintaining the physiologic pressure column. The reasons for this are many but include unfamiliarity with the central nervous system and the historical risks that continue to overshadow the low complication rates in modern clinical series., Materials and Methods: Our intent in this review is to explore the access devices currently on the market, assess the risk associated with breaching the intrathecal space, and propose a research model for bringing to patients the next generation of intrathecal hardware. For this purpose, we reviewed both historical and contemporary literature that pertains to the access devices and catheters intended for both temporary and permanent implantation and the complications thereof., Results: There are few devices that are currently marketed in the United States or Europe for intrathecal use. Most hew to a relatively fixed design pattern predicated on the dimensions and properties of the thecal sac. All are typically composed of soft silicone, and employ a Tuohy needle for access despite design limitations. In general, these catheters are engineered for durability, ease of use, and regional deployment. Devices on the market with steerability or targeted intrathecal fixation are not yet available. Complications, once a legitimate concern, are now quite rare when recommended techniques are followed., Conclusions: Over the next decade, advances in intrathecal catheter design, access techniques, imaging, and greater understanding of the spinal cord neurophysiology will usher in an era where the intrathecal space is recognized as a highly valued diagnostic and therapeutic target. We anticipate that this will occur in several concurrent phases, each with the potential to accelerate the growth of the others., (© 2017 International Neuromodulation Society.)

Introduction: Accurate electrode implantation is a major goal of deep brain stimulation (DBS) surgery. Intraoperative physiology with microelectrode recording (MER) is routinely used to refine stereotactic accuracy during awake electrode implantation. Recently, portable imaging systems such as the O-arm have become widely available and can be used in isolation or in association with MER to guide DBS lead placement. The aim of this study was to evaluate how the routine use of the O-arm affected DBS surgery safety, efficiency, and outcomes., Methods: Two cohorts of patients with Parkinson's disease who underwent MER-guided awake subthalamic DBS lead implantation with and without O-arm were compared. We examined the total number of microelectrode and macroeletrode passes during each surgery, procedure duration, surgical complications, lead revisions, and motor outcomes., Results: A total of 50 procedures in 41 unique patients were analyzed, of which 26 were performed without O-arm and 24 performed without the O-arm. The mean number of microelectrode passes was 2.46 (SD = 0.99) in the group without O-arm utilization, compared to 1.29 (SD = 0.75) in the group with O-arm usage (p < 0.001). A significant reduction was also found in procedure duration (p = 0.016). No differences were found in motor outcomes between groups., Conclusion: The use of the O-arm during DBS lead implantation was associated with significantly fewer brain cannulations for microelectrode recording as well as reduced surgical time., (© 2017 International Neuromodulation Society.)

Ischemic stroke is a leading cause of disability worldwide, with profound economic costs. Poststroke motor impairment is the most commonly encountered deficit resulting in significant disability and is the primary driver of stroke-associated healthcare expenditures. Although many patients derive some degree of benefit from physical rehabilitation, a significant proportion continue to suffer from persistent motor impairment. Noninvasive brain stimulation, vagal nerve stimulation, epidural cortical stimulation, and deep brain stimulation (DBS) have all been studied as potential modalities to improve upon the benefits derived from physical therapy alone. These neuromodulatory therapies aim primarily to augment neuroplasticity and drive functional reorganization of the surviving perilesional cortex. The authors have proposed a novel and emerging therapeutic approach based on cerebellar DBS targeted at the dentate nucleus. Their rationale is based on the extensive reciprocal connectivity between the dentate nucleus and wide swaths of cerebral cortex via the dentatothalamocortical and corticopontocerebellar tracts, as well as the known limitations to motor rehabilitation imposed by crossed cerebellar diaschisis. Preclinical studies in rodent models of ischemic stroke have shown that cerebellar DBS promotes functional recovery in a frequency-dependent manner, with the most substantial benefits of the therapy noted at 30-Hz stimulation. The improvements in motor function are paralleled by increased expression of markers of synaptic plasticity, synaptogenesis, and neurogenesis in the perilesional cortex. Given the findings of preclinical studies, a first-in-human trial, Electrical Stimulation of the Dentate Nucleus Area (EDEN) for Improvement of Upper Extremity Hemiparesis Due to Ischemic Stroke: A Safety and Feasibility Study, commenced in 2016. Although the existing preclinical evidence is promising, the results of this Phase I trial and subsequent clinical trials will be necessary to determine the future applicability of this therapy.

Objective: Spinal cord stimulation (SCS) is a safe, reversible surgical treatment for complex regional pain syndrome and failed back surgery syndrome refractory to conventional medical management. Paddle electrodes are routinely used for the permanent implant because of the reduced risk of migration, lower energy requirements, and expanded coverage options. The risks associated with paddle lead removal are not well defined in the literature., Methods: We retrospectively reviewed the outcomes of all patients at the Cleveland Clinic who underwent removal of SCS paddle electrodes between 2009 and 2016., Results: We identified 68 patients during this interval who had a paddle electrode removed. The most common reason for removal was loss of coverage or effect (75%), followed by infection (13.24%), and the need for magnetic resonance imaging for diagnostic purposes (8.82%). Postoperative complications occurred in eight patients (11.75%), two of which were classified as major (2.94%). One of these patients developed a postoperative cerebrospinal fluid leak, and another suffered a large suprafascial hematoma. Both patients underwent reoperation. Minor complications were reported in six patients (8.82%) and included wound dehiscence, infection, and prolonged ileus in one case. On average, patients who developed complications lost 20 mL more blood during surgery than those who did not develop complications (p = 0.006)., Conclusion: One of the benefits of SCS therapy is the reversibility of the procedure. However, removal is not without some risk though the overall risk of minor or major complication is low. Patients who are considering removal should be counseled appropriately. Prophylactic removal is not recommended. However, when removal is needed, surgeons and pain specialists must be familiar with these complications and their management., (© 2017 International Neuromodulation Society.)

Objective: The number of patients who benefit from deep brain stimulation (DBS) for Parkinson's disease (PD) has increased significantly since the therapy was first approved by the FDA. Suboptimal outcomes, infection, or device failure are risks of the procedure and may require lead removal or repositioning. The authors present here the results of their series of revision and reimplantation surgeries., Methods: The data were reviewed from all DBS intracranial lead removals, revisions, or reimplantations among patients with PD over a 6-year period at the authors' institution. The indications for these procedures were categorized as infection, suboptimal outcome, and device failure. Motor outcomes as well as lead location were analyzed before removal and after reimplant or revision., Results: The final sample included 25 patients who underwent 34 lead removals. Thirteen patients had 18 leads reimplanted after removal. There was significant improvement in the motor scores after revision surgery among the patients who had the lead revised for a suboptimal outcome (p = 0.025). The mean vector distance of the new lead location compared to the previous location was 2.16 mm (SD 1.17), measured on an axial plane 3.5 mm below the anterior commissure-posterior commissure line. When these leads were analyzed by subgroup, the mean distance was 1.67 mm (SD 0.83 mm) among patients treated for infection and 2.73 mm (SD 1.31 mm) for those with suboptimal outcomes., Conclusions: Patients with PD who undergo reimplantation surgery due to suboptimal outcome may experience significant benefits. Reimplantation after surgical infection seems feasible and overall safe.

Background: Brain shift and pneumocephalus are major concerns regarding deep brain stimulation (DBS)., Objective: To report the extent of brain shift in deep structures and pneumocephalus in intraoperative magnetic resonance imaging (MRI)., Methods: Twenty patients underwent bilateral DBS implantation in an MRI suite. Volume of pneumocephalus, duration of procedure, and 6 anatomic landmarks (anterior commissure, posterior commissure, right fornix [RF], left fornix [LF], right putaminal point, and left putaminal point) were measured., Results: Pneumocephalus varied from 0 to 32 mL (median = 0.6 mL). Duration of the procedure was on average 195.5 min (118-268 min) and was not correlated with the amount of pneumocephalus. There was a significant posterior displacement of the anterior commissure (mean = -1.1 mm, P < .001), RF (mean = -0.6 mm, P < .001), LF (mean = -0.7 mm, P < .001), right putaminal point (mean = -0.9 mm, P = .001), and left putaminal point (mean = -1.0 mm, P = .001), but not of the posterior commissure (mean = 0.0 mm, P = .85). Both RF (mean = -.7 mm, P < .001) and LF (mean = -0.5 mm, P < .001) were posteriorly displaced after a right-sided burr hole. There was a correlation between anatomic landmarks displacement and pneumocephalus after 2 burr holes (rho = 0.61, P = .007), but not after 1 burr hole (rho = 0.16, P = .60)., Conclusion: Better understanding of how pneumocephalus displaces subcortical structures can significantly enhance our intraoperative decision making and overall targeting strategy.

Infections are one of the most common causes of mortality in immunocompromised patients. In patients diagnosed with hematologic malignancies, treatment with stem cell transplants (SCT) or T-cell suppressing chemotherapy increases the risk of central nervous system (CNS) infections, of which toxoplasmosis is the most common. We report the case of a 63 year-old woman with chronic lymphocytic leukemia (CLL) that presented with gait instability and visual changes. Intracranial lesions were noted on initial neuro-imaging. A rapid decline in the patient's mental status warranted an urgent biopsy of the lesions that revealed tachyzoites consistent with toxoplasmosis. In the presence of diffuse brain lesions that lack a metastatic pattern or contrast enhancement, a common approach is to perform biopsy only after a battery of non-invasive testing. This diagnostic delay may take several days, exposing the patient to a rapidly fatal infection. This report illustrates the utility of early brain biopsy in high-risk patients with hematologic malignancies and CNS lesions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Understanding the relevant biophysical properties of the spinal dura mater is essential to the design of medical devices that will directly interact with this membrane or influence the contents of the intradural space. We searched the literature and reviewed the pertinent characteristics for the design, construction, testing, and imaging of novel devices intended to perforate, integrate, adhere or reside within or outside of the spinal dura mater. The spinal dura mater is a thin tubular membrane composed of collagen and elastin fibres that varies in circumference along its length. Its mechanical properties have been well-described, with the longitudinal tensile strength exceeding the transverse strength. Data on the bioelectric, biomagnetic, optical and thermal characteristics of the spinal dura are limited and sometimes taken to be similar to those of water. While various modalities are available to visualise the spinal dura, magnetic resonance remains the best modality to segment its structure. The reaction of the spinal dura to imposition of a foreign body or other manipulations of it may compromise its biomechanical and immune-protective benefits. Therefore, dural sealants and replacements are of particular clinical, research and commercial interest. In conclusion, existing devices that are in clinical use for spinal cord stimulation, intrathecal access or intradural implantation largely adhere to traditional designs and their attendant limitations. However, if future devices are built with an understanding of the dura's properties incorporated more fully into the designs, there is potential for improved performance.

Introduction: Deep brain stimulation (DBS) is a well-recognized treatment for patients with movement disorders and other neurological diseases. The implantable pulse generator (IPG) is a fundamental component of the DBS system. Although IPG implantation and replacement surgeries are comparatively minor procedures relative to the brain lead insertion, patients often require multiple IPG replacements during their lifetime with each operation carrying a small but possibly cumulative risk of complications. To better educate our patients and improve surgical outcomes, we reviewed our series of patients at our institution., Methods: Using electronic health record data, we retrospectively reviewed all initial and subsequent IPG surgeries from patients who underwent at least one IPG surgery between the years of 2010 and 2015 at the Cleveland Clinic main campus. We calculated infection rates for initial IPG implantation surgeries and the infection rate for subsequent replacements. Fisher's exact tests were used to evaluate the chance of an infection between the initial implantation and replacement. Fisher's exact tests and simple logistic regression analyses were used to determine the predictive ability of selected demographic and clinical variables RESULTS: Our final sample included 697 patients and 1537 surgeries. For all patients, the infection rate at the first surgery was 2.01%; at the second surgery, it was 0.44%; and at the third surgery, it was 1.83%. When considering only patients that underwent at least three replacement surgeries (n = 114) the infection rate did not change in a significant manner with subsequent interventions compared to the first replacement. No other variable of interest was a significant predictor of infection., Conclusion: We did not find increasing rates of infection with subsequent IPG replacement procedures., (© 2017 International Neuromodulation Society.)