Faculty Bibliography

The introduction of peripheral neuromodulation to treat headache and facial pain two decades ago opened up the field to non-neurosurgical practitioners, given the relatively low risk and technical ease of the procedure. These procedures, primarily occipital nerve stimulation (ONS) and trigeminal branch stimulation such as supra- and infraorbital nerve stimulation, are now established to be effective in a number of facial pain and headache syndromes, despite their lack of approval by regulatory agencies such as the US Food and Drug Administration (FDA). For that reason and others, dedicated hardware for these procedures has not yet been developed, thus relying on hardware designed for placement in the epidural space for spinal cord stimulation (SCS). This has led to a series of technical issues and device-related complications not traditionally seen with SCS. I will review the surgical technique of ONS and peripheral nerve stimulation of the head and face utilizing this equipment, and discuss methods learned by experienced practitioners over the years to minimize device-related complications.

Deep brain stimulation may be an effective therapy for select cases of severe, treatment-refractory Tourette syndrome; however, patient responses are variable, and there are no reliable methods to predict clinical outcomes. The objectives of this retrospective study were to identify the stimulation-dependent structural networks associated with improvements in tics and comorbid obsessive-compulsive behaviour, compare the networks across surgical targets, and determine if connectivity could be used to predict clinical outcomes. Volumes of tissue activated for a large multisite cohort of patients (n = 66) implanted bilaterally in globus pallidus internus (n = 34) or centromedial thalamus (n = 32) were used to generate probabilistic tractography to form a normative structural connectome. The tractography maps were used to identify networks that were correlated with improvement in tics or comorbid obsessive-compulsive behaviour and to predict clinical outcomes across the cohort. The correlated networks were then used to generate 'reverse' tractography to parcellate the total volume of stimulation across all patients to identify local regions to target or avoid. The results showed that for globus pallidus internus, connectivity to limbic networks, associative networks, caudate, thalamus, and cerebellum was positively correlated with improvement in tics; the model predicted clinical improvement scores (P = 0.003) and was robust to cross-validation. Regions near the anteromedial pallidum exhibited higher connectivity to the positively correlated networks than posteroventral pallidum, and volume of tissue activated overlap with this map was significantly correlated with tic improvement (P < 0.017). For centromedial thalamus, connectivity to sensorimotor networks, parietal-temporal-occipital networks, putamen, and cerebellum was positively correlated with tic improvement; the model predicted clinical improvement scores (P = 0.012) and was robust to cross-validation. Regions in the anterior/lateral centromedial thalamus exhibited higher connectivity to the positively correlated networks, but volume of tissue activated overlap with this map did not predict improvement (P > 0.23). For obsessive-compulsive behaviour, both targets showed that connectivity to the prefrontal cortex, orbitofrontal cortex, and cingulate cortex was positively correlated with improvement; however, only the centromedial thalamus maps predicted clinical outcomes across the cohort (P = 0.034), but the model was not robust to cross-validation. Collectively, the results demonstrate that the structural connectivity of the site of stimulation are likely important for mediating symptom improvement, and the networks involved in tic improvement may differ across surgical targets. These networks provide important insight on potential mechanisms and could be used to guide lead placement and stimulation parameter selection, as well as refine targets for neuromodulation therapies for Tourette syndrome.

OBJECTIVE:To conduct a systematic literature review of dorsal root ganglion (DRG) stimulation for pain. DESIGN/METHODS:Grade the evidence for DRG stimulation. METHODS:An international, interdisciplinary work group conducted a literature search for DRG stimulation. Abstracts were reviewed to select studies for grading. General inclusion criteria were prospective trials (randomized controlled trials and observational studies) that were not part of a larger or previously reported group. Excluded studies were retrospective, too small, or existed only as abstracts. Studies were graded using the modified Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria. RESULTS:DRG stimulation has Level II evidence (moderate) based upon one high-quality pivotal randomized controlled trial and two lower-quality studies. CONCLUSIONS:Moderate-level evidence supports DRG stimulation for treating chronic focal neuropathic pain and complex regional pain syndrome.

INTRODUCTION/BACKGROUND:Tourette syndrome (TS) is a complex neuropsychiatric disorder. A small percentage of individuals with TS can experience persistent severe, refractory, and impairing tics. Deep brain stimulation (DBS) has been increasingly used for symptom management, especially in these settings. In this article, we aim to evaluate the rate and the reasons for removal of DBS hardware in TS patients. METHODS:Data was analyzed from patients enrolled in the Tourette Association of America's International Tourette Syndrome Registry and Database. RESULTS:Fifteen of 269 (5.6%) patients required removal of their DBS systems. The mean age at explantation was 33.8 years. In these cases we observed a rate of 1.9 explantations per year of follow up from implantation. None of the removals took place in the immediate post-operative period. Infection was the most common cause (46.7%). Only one patient received explantation for tic resolution. There were no significant associations between explantation and the presence of specific psychiatric comorbidities, including OCD, depression, anxiety, or ADHD. DISCUSSION/CONCLUSIONS:The rate of removal of 5.6% was lower than the previously reported rate in the TS DBS literature. Infections accounted for nearly half of the TS DBS explantations in this cohort. There was no relationship to psychiatric comorbidities.

BACKGROUND:Deep brain stimulation (DBS) of the subthalamic nucleus is an established therapeutic option for managing motor symptoms of Parkinson's disease. We conducted a double-blind, sham-controlled, randomised controlled trial to assess subthalamic nucleus DBS, with a novel multiple independent contact current-controlled (MICC) device, in patients with Parkinson's disease. METHODS:This trial took place at 23 implanting centres in the USA. Key inclusion criteria were age between 22 and 75 years, a diagnosis of idiopathic Parkinson's disease with over 5 years of motor symptoms, and stable use of anti-parkinsonian medications for 28 days before consent. Patients who passed screening criteria were implanted with the DBS device bilaterally in the subthalamic nucleus. Patients were randomly assigned in a 3:1 ratio to receive either active therapeutic stimulation settings (active group) or subtherapeutic stimulation settings (control group) for the 3-month blinded period. Randomisation took place with a computer-generated data capture system using a pre-generated randomisation table, stratified by site with random permuted blocks. During the 3-month blinded period, both patients and the assessors were masked to the treatment group while the unmasked programmer was responsible for programming and optimisation of device settings. The primary outcome was the difference in mean change from baseline visit to 3 months post-randomisation between the active and control groups in the mean number of waking hours per day with good symptom control and no troublesome dyskinesias, with no increase in anti-parkinsonian medications. Upon completion of the blinded phase, all patients received active treatment in the open-label period for up to 5 years. Primary and secondary outcomes were analysed by intention to treat. All patients who provided informed consent were included in the safety analysis. The open-label phase is ongoing with no new enrolment, and current findings are based on the prespecified interim analysis of the first 160 randomly assigned patients. The study is registered with ClinicalTrials.gov, NCT01839396. FINDINGS/RESULTS:Between May 17, 2013, and Nov 30, 2017, 313 patients were enrolled across 23 sites. Of these 313 patients, 196 (63%) received the DBS implant and 191 (61%) were randomly assigned. Of the 160 patients included in the interim analysis, 121 (76%) were randomly assigned to the active group and 39 (24%) to the control group. The difference in mean change from the baseline visit (post-implant) to 3 months post-randomisation in increased ON time without troublesome dyskinesias between the active and control groups was 3·03 h (SD 4·52, 95% CI 1·3-4·7; p<0·0001). 26 serious adverse events in 20 (13%) patients occurred during the 3-month blinded period. Of these, 18 events were reported in the active group and 8 in the control group. One death was reported among the 196 patients before randomisation, which was unrelated to the procedure, device, or stimulation. INTERPRETATION/CONCLUSIONS:This double-blind, sham-controlled, randomised controlled trial provides class I evidence of the safety and clinical efficacy of subthalamic nucleus DBS with a novel MICC device for the treatment of motor symptoms of Parkinson's disease. Future trials are needed to investigate potential benefits of producing a more defined current field using MICC technology, and its effect on clinical outcomes. FUNDING/BACKGROUND:Boston Scientific.

INTRODUCTION/BACKGROUND:Deep brain stimulation (DBS) targeting the subthalamic nucleus (STN) has been shown to reliably improve several symptoms of Parkinson's disease (PD) in appropriately selected patients. Various factors may preclude patients from undergoing DBS and for them, non-invasive lesion-based therapies such as focused ultrasound and Gamma Knife (GK) radiosurgery may present a safer alternative. MATERIALS AND METHODS/METHODS:Based on preliminary positive reports of STN GK for PD, we conducted a prospective, open-label, single-center, pilot study in PD patients deemed potential candidates for unilateral DBS based on their disease characteristics, but contraindicated due to age >74, an irreversible bleeding diathesis, or significant comorbid medical disease. Stereotactic MRI-guided GK radiosurgery was performed using a single 110- or 120-Gy dose targeting the STN contralateral to the more symptomatic extremity. Clinical follow-up and imaging assessed the safety and efficacy of the procedure over a 12-month period. RESULTS:Four PD patients with medication-refractory tremors and disabling dyskinesias underwent unilateral STN GK radiosurgery. Contraindications to DBS included high-risk comorbid cardiovas-cular disease in 3 patients and an irreversible bleeding diathesis in 1. There were no immediate post-procedural adverse events. One patient who underwent left STN GK radiosurgery developed right hemiparesis and dysarthria 7 months post-procedure followed by hospitalization at 9 months for bacterial endocarditis and liver failure from which he died. The remaining 3 patients were free of adverse events up to 12 months post-procedure and experienced a reduction in contralateral rigidity, bradykinesia, and tremor. Upon extended follow-up, 2 patients developed subacute worsening of gait. One died at 16 months due to complications of a fall whereas the other saw no change in gait up to 42 months post-procedure. All 3 patients with adverse events demonstrated a hyper-response in the targeted area on follow-up neuroimaging. DISCUSSION/CONCLUSION/CONCLUSIONS:Despite the potential for clinical improvement, our results suggest that unilateral STN GK radiosurgery should be approached cautiously in medically frail PD patients who may be at higher risk of GK hyper-response and neurologic complications.

INTRODUCTION/BACKGROUND:Dorsal root ganglion (DRG) stimulation has been established as a therapy in the treatment of chronic pain. Ideal electrode placement is guided by proper identification of the location of the DRG. The location of the S1 DRG is not well delineated and can be variable making ideal location of the electrode placement difficult based on fluoroscopic imaging. METHODS:This is a retrospective analysis of postoperative programming of S1 DRG leading across two centers. There were 34 lead placements in 24 patients included in this study. Programming parameters and contacts used were evaluated based on the position of the electrode in reference to the sacral border. RESULTS:The majority of the patient programming parameters were recorded at six weeks following the implant. Most commonly, the programming used a simple continuous bipole configuration. Of the 34 leads programmed, 17 (50%) had programming on the sacral border, 14 (41%) were considered posterior, and 3 (9%) were anterior to the sacral border. CONCLUSION/CONCLUSIONS:This analysis of S1 DRG programming demonstrates that ideal positioning of the majority of the contacts for the electrode should be posterior and along the sacral border on fluoroscopic imaging. These findings also suggest that the S1 DRG may be located most reproducibly at the border of the intraforaminal and intracanalicular region.

BACKGROUND:Deep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting. METHODS:We collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases. RESULTS:Tics and obsessive-compulsive behaviour (OCB) significantly improved over time (p<0.01), and there were no significant differences across brain targets (p>0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi. CONCLUSION/CONCLUSIONS:The results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.

BACKGROUND AND PURPOSE/OBJECTIVE:The basal forebrain contains multiple structures of great interest to emerging functional neurosurgery applications, yet many neuroradiologists are unfamiliar with this neuroanatomy because it is not resolved with current clinical MR imaging. MATERIALS AND METHODS/METHODS:= 13) to demonstrate and characterize the detailed anatomy of the basal forebrain using a clinical 3T MR imaging scanner. We measured the size of selected internal myelinated pathways and measured subthalamic nucleus size, oblique orientation, and position relative to the intercommissural point. RESULTS:= .084 and .047, respectively). Individual variability for the subthalamic nucleus was greatest for angulation within the sagittal plane (range, 15°-37°), transverse dimension (range, 2-6.7 mm), and most inferior border (range, 4-7 mm below the intercommissural plane). CONCLUSIONS:Direct identification of basal forebrain structures in multiple planes using the TSE T2 sequence makes this challenging neuroanatomy more accessible to practicing neuroradiologists. This protocol can be used to better define individual variations relevant to functional neurosurgical targeting and validate/complement advanced MR imaging methods being developed for direct visualization of these structures in living patients.

Decisions are made through the integration of external and internal inputs until a threshold is reached, triggering a response. The subthalamic nucleus (STN) has been implicated in adjusting the decision bound to prevent impulsivity during difficult decisions. We combine model-based and model-free approaches to test the theory that the STN raises the decision bound, a process impaired by deep brain stimulation (DBS). Eight male and female human subjects receiving treatment for Parkinson's disease with bilateral DBS of the STN performed an auditory two-alternative forced choice task. By ending trials unpredictably, we collected reaction time (RT) trials in which subjects reached their decision bound and non-RT trials in which subjects were forced to make a decision with less evidence. A decreased decision bound would cause worse performance on RT trials, and we found this to be the case on left-sided RT trials. Drift diffusion modeling showed a negative drift rate. This implies that in the absence of new evidence, the amount of evidence accumulated tends to drift toward zero. If evidence is accumulated at a constant rate this results in the evidence accumulated reaching an asymptote, the distance of which from the bound was decreased by DBS (p = 0.0079, random shuffle test), preventing subjects from controlling impulsivity. Subjects were more impulsive to bursts of stimuli associated with conflict (p < 0.001, cluster mass test). In addition, DBS lowered the decision bound specifically after error trials, decreasing the probability of switching to a non-RT trial after an error compared to correct response (28% vs. 38%, p = 0.005, Fisher exact test). The STN appears to function in decision-making by modulating the decision bound and drift rate to allow the suppression of impulsive responses.