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Background: Corpus callosotomy for medically intractable epilepsy is an effective ablative procedure traditionally achieved using either standard open craniotomy or with less-invasive approaches. Advances in robotic-assisted stereotactic guidance for neurosurgery can be applied for LITT for corpus callosotomy. Clinical Presentations: Two patients were included in this study. One was a 25-year-old female patient with extensive bi-hemispheric malformations of cortical development and medically refractory epilepsy, and the other was an 18-year-old male with medically refractory epilepsy and atonic seizures, who underwent a complete corpus callosotomy using robotic-assisted stereotactic guidance for LITT. Results: Both patients underwent successful intended corpus callosotomy with volumetric analysis demonstrating a length disconnection of 74% and a volume disconnection of 55% for patient 1 and a length disconnection of 83% and a volume disconnection of 33% for patient 2. Postoperatively, both patients had clinical reductions in seizure. Conclusion: Our experience demonstrates that robotic guidance systems can safely and effectively be adapted for minimally invasive LITT corpus callosotomy.

OBJECTIVE Despite recently heightened advocacy efforts relating to pregnancy and family leave policies in multiple surgical specialties, no studies to date have described female neurosurgeons’ experiences with childbearing. The AANS/CNS Section of Women in Neurosurgery created the Women and Pregnancy Task Force to ascertain female neurosurgeons’ experiences with and attitudes toward pregnancy and the role of family leave policies. METHODS A voluntary online 28-question survey examined the pregnancy experiences of female neurosurgeons and perceived barriers to childbearing. The survey was developed and electronically distributed to all members of the American Association of Neurological Surgeons and Congress of Neurological Surgeons who self-identified as female in February 2016. Responses from female resident physicians, fellows, and current or retired practicing neurosurgeons were analyzed. RESULTS A total of 126 women (20.3%) responded to the survey; 57 participants (49%) already had children, and 39 (33%) planned to do so. Participants overwhelmingly had or planned to have children during the early practice and senior residency years. The most frequent obstacles experienced or anticipated included insufficient time to care for newborns (47% of women with children, 92% of women planning to have children), discrimination by coworkers (31% and 77%, respectively), and inadequate time for completion of board requirements (18% and 51%, respectively). There was substantial variability in family leave policies, and a minority of participants (35%) endorsed the presence of any formal policy at their institution. Respondents described myriad unique challenges associated with pregnancy and family leave. CONCLUSIONS Pregnancy and family leave pose significant challenges to the recruitment, retention, and advancement of women in neurosurgery. It is thus imperative to promote clear family leave policies for trainees and practitioners, address discrimination surrounding these topics, and encourage forethought and flexibility to tackle obstacles inherent in pregnancy and the early stages of child rearing.

Background: Deep brain stimulation (DBS) is an effective surgical treatment for movement disorders. Early versions of implantable systems delivered stimulation with constant voltage (CV); however, advances in available and newer platforms have permitted programming in constant current (CC). From a treatment management perspective, there are theoretical advantages of CC stimulation. In this case series, we present clinical evidence supporting the maintenance of current regardless of changes to impedance. Materials and Methods: This case series included 3 patients with Parkinson’s disease status post-bilateral subthalamic nucleus DBS. Patients in this series self-reported intermittent diplopia with pressure applied to the scalp. Patients were subsequently examined and converted from CV to CC and re-examined. Impedances were checked prior to and after conversion from CV to CC as well as while applying pressure to the scalp that induced the adverse effects. Results: Across patients, we observed that compression of the scalp overlying the connector, while patients were maintained in CV, consistently and objectively induced unilateral adduction of an eye. In addition, during scalp compression, while in CV, impedance was reduced, which would increase current delivery. Converting the patients to CC stimulation without changing other stimulation parameters eliminated diplopia and objective findings of eye deviation with compression of the scalp overlying the hardware despite changes in impedance. Conclusions: In this case series, we provide clinical support for the principal differences between CV and CC stimulation.

ObjectivesDeep brain stimulation (DBS), targeting the subthalamic nucleus (STN) and globus pallidus interna, is a surgical therapy with class 1 evidence for Parkinson’s disease (PD). Bilateral DBS electrodes may be implanted within a single operation or in separate staged surgeries with an interval of time that varies patient by patient. In this study, we used the variation in the timing of implantation from the first to the second implantation allowing for examination of potential volumetric changes of the basal ganglia in patients with PD who underwent staged STN DBS.MethodsThirty-two patients with a mean time interval between implantations of 141.8 (±209.1; range: 7–700) days and mean duration of unilateral stimulation of 244.7 (±227.7; range: 20–672) days were included in this study. Using volumetric analysis of whole hemisphere and subcortical structures, we observed whether implantation or stimulation affected structural volume.ResultsWe observed that DBS implantation, but not the duration of stimulation, induced a significant reduction of volume in the caudate, pallidum, putamen and thalamus ipsilateral to the implanted hemisphere. These findings were not dependent on the trajectory of the implanted electrode nor on first surgery pneumocephalus (0.07%: %Δ for intracranial volume between first and second surgery). In addition, unique regional atrophy differences were evident in each of the structures.ConclusionOur results demonstrate that DBS implantation surgery may affect hemisphere volume at the level of subcortical structures connected to the surgical target.

ObjectiveThe severity of motor symptoms in Parkinson’s disease (PD) depends on environmental conditions. For example, the presence of external patterns such as a rhythmic tone can attenuate bradykinetic impairments. However, the neural mechanisms for this context-dependent attenuation (e.g., paradoxical kinesis) remain unknown. Here, we investigate whether context-dependent symptom attenuation is reflected in single-unit activity recorded in the operating room from the substantia nigra pars reticulata (SNr) of patients with PD undergoing deep brain stimulation surgery. The SNr is known to influence motor planning and execution in animal models, but its role in humans remains understudied.MethodsWe recorded SNr activity while subjects performed cued directional movements in response to auditory stimuli under interleaved ‘patterned’ and ‘unpatterned’ contexts. SNr localisation was independently confirmed with expert intraoperative assessment as well as post hoc imaging-based reconstructions.ResultsAs predicted, we found that motor performance was improved in the patterned context, reflected in increased reaction speed and accuracy compared with the unpatterned context. These behavioural differences were associated with enhanced responsiveness of SNr neurons—that is, larger changes in activity from baseline—in the patterned context. Unsupervised clustering analysis revealed two distinct subtypes of SNr neurons: one exhibited context-dependent enhanced responsiveness exclusively during movement preparation, whereas the other showed enhanced responsiveness during portions of the task associated with both motor and non-motor processes.ConclusionsOur findings indicate the SNr participates in motor planning and execution, as well as warrants greater attention in the study of human sensorimotor integration and as a target for neuromodulatory therapies.

Introduction: Deep brain stimulation of the zona incerta is effective at treating tremor and other forms of parkinsonism. However, the structure is not well visualized with standard MRI protocols making direct surgical targeting unfeasible and contributing to inconsistent clinical outcomes. In this study, we applied coronal gradient echo MRI to directly visualize the rostral zona incerta in Parkinson’s disease patients to improve targeting for deep brain stimulation. Methods: We conducted a prospective study to optimize and evaluate an MRI sequence to visualize the rostral zona incerta in patients with Parkinson’s disease (n = 31) and other movement disorders (n = 13). We performed a contrast-to-noise ratio analysis of specific regions of interest to quantitatively assess visual discrimination of relevant deep brain structures in the optimized MRI sequence. Regions of interest were independently assessed by 2 neuroradiologists, and interrater reliability was assessed. Results: Rostral zona incerta and subthalamic nucleus were well delineated in our 5.5-min MRI sequence, indicated by excellent interrater agreement between neuroradiologists for region-of-interest measurements (>0.90 intraclass coefficient). Mean contrast-to-noise ratio was high for both rostral zona incerta (6.39 ± 3.37) and subthalamic nucleus (17.27 ± 5.61) relative to adjacent white matter. There was no significant difference between mean signal intensities or contrast-to-noise ratio for Parkinson’s and non-Parkinson’s patients for either structure. Discussion/Conclusion: Our optimized coronal gradient echo MRI sequence delineates subcortical structures relevant to traditional and novel deep brain stimulation targets, including the zona incerta, with high contrast-to-noise. Future studies will prospectively apply this sequence to surgical planning and postimplantation outcomes.

Responsive neurostimulation (RNS) for intractable epilepsy involves placement of electrodes onto or into the brain that detect seizure activity and then deliver a current to abort a seizure before it spreads. Successful RNS treatment can deliver hundreds of stimulations per day, which are generally unnoticeable to patients. Uncommonly, RNS electrodes may result in stimulation of brain regions or peripheral structures that causes uncomfortable sensory or motor effects, a phenomenon we refer to as stimulation-triggered signs or symptoms (STS). Occurrence of STS may limit the ability to use RNS to full capacity to reduce seizures. In this case series, we describe STS in six out of 58 (10.3%) RNS patients at our institution. To eliminate or minimize STS, we developed a protocol for modification of RNS parameters. Modifying RNS stimulation was associated with reduced STS in all six patients, five had adjustment of stimulation settings, one of lead position. Five out of six patients were able to undergo further optimization of RNS for improved seizure control after reduction of symptoms. One patient had recurrent STS that prevented further increase of RNS stimulation current. This study may help other medical teams in identifying and reducing STS in patients with epilepsy receiving RNS devices.

Objective This study aimed to compare seizure outcomes and complication rates in patients treated with only responsive neurostimulation (RNS) strip leads with those treated with only RNS depth leads. Methods A retrospective cohort study was performed using the institutional epilepsy surgery database. Included was any patient implanted with the RNS system between August 2015 and May 2018 with either two depth (2D) or two strip (2S) leads connected to the device and at least 6 months follow-up. Excluded were those with a combination of active depth and strip leads. Data extracted from the charts comprised demographic information, duration of epilepsy, presence of a magnetic resonance imaging (MRI) lesion, prior resective surgery, clinically disabling seizures at baseline and follow-up, prior invasive monitoring, location (mesial temporal or neocortical) and number of seizure foci, unilateral or bilateral RNS lead placement, and postoperative complications. Results Of 48 screened patients, 34 met study inclusion criteria. Of these, 15 were treated with 2D leads and 19 with 2S leads. Groups 2D and 2S were comparable with respect to age at onset, duration of epilepsy, baseline seizure frequency, and exposure time to RNS. After adjustment for patient age and duration of epilepsy, seizure frequency in 2S patients was noted to be decreased by 83% (p = 0.046), while it was reduced by 51% (p = 0.080) in 2D patients. The complication rate was not significantly different between the two groups. Conclusion In our small retrospective population, patients with RNS strip leads experienced a significantly greater seizure reduction than patients with RNS depth leads, without a difference in complication rate.

ObjectiveRefractory psychiatric disease is a major cause of morbidity and mortality worldwide, and there is a great need for new treatments. In the last decade, investigators piloted novel deep brain stimulation (DBS)-based therapies for depression and obsessive–compulsive disorder (OCD). Results from recent pivotal trials of these therapies, however, did not demonstrate the degree of efficacy expected from previous smaller trials. To discuss next steps, neurosurgeons, neurologists, psychiatrists and representatives from industry convened a workshop sponsored by the American Society for Stereotactic and Functional Neurosurgery in Chicago, Illinois, in June of 2016.DesignHere we summarise the proceedings of the workshop. Participants discussed a number of issues of importance to the community. First, we discussed how to interpret results from the recent pivotal trials of DBS for OCD and depression. We then reviewed what can be learnt from lesions and closed-loop neurostimulation. Subsequently, representatives from the National Institutes of Health, the Food and Drug Administration and industry discussed their views on neuromodulation for psychiatric disorders. In particular, these third parties discussed their criteria for moving forward with new trials. Finally, we discussed the best way of confirming safety and efficacy of these therapies, including registries and clinical trial design. We close by discussing next steps in the journey to new neuromodulatory therapies for these devastating illnesses.ConclusionInterest and motivation remain strong for deep brain stimulation for psychiatric disease. Progress will require coordinated efforts by all stakeholders.

Summary Background Deep brain stimulation (DBS) of the subcallosal cingulate white matter has shown promise as an intervention for patients with chronic, unremitting depression. To test the safety and efficacy of DBS for treatment-resistant depression, a prospective, randomised, sham-controlled trial was conducted. Methods Participants with treatment-resistant depression were implanted with a DBS system targeting bilateral subcallosal cingulate white matter and randomised to 6 months of active or sham DBS, followed by 6 months of open-label subcallosal cingulate DBS. Randomisation was computer generated with a block size of three at each site before the site started the study. The primary outcome was frequency of response (defined as a 40% or greater reduction in depression severity from baseline) averaged over months 4–6 of the double-blind phase. A futility analysis was performed when approximately half of the proposed sample received DBS implantation and completed the double-blind phase. At the conclusion of the 12-month study, a subset of patients were followed up for up to 24 months. The study is registered at ClinicalTrials.gov, number NCT00617162. Findings Before the futility analysis, 90 participants were randomly assigned to active (n=60) or sham (n=30) stimulation between April 10, 2008, and Nov 21, 2012. Both groups showed improvement, but there was no statistically significant difference in response during the double-blind, sham-controlled phase (12 [20%] patients in the stimulation group vs five [17%] patients in the control group). 28 patients experienced 40 serious adverse events; eight of these (in seven patients) were deemed to be related to the study device or surgery. Interpretation This study confirmed the safety and feasibility of subcallosal cingulate DBS as a treatment for treatment-resistant depression but did not show statistically significant antidepressant efficacy in a 6-month double-blind, sham-controlled trial. Future studies are needed to investigate factors such as clinical features or electrode placement that might improve efficacy. Funding Abbott (previously St Jude Medical).

Sleep is a fundamental homeostatic process, and disorders of sleep can greatly affect quality of life. Parkinson’s disease (PD) is highly comorbid for a spectrum of sleep disorders and deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been reported to improve sleep architecture in PD. We studied local field potential (LFP) recordings in PD subjects undergoing STN-DBS over the course of a full-night’s sleep. We examined the changes in oscillatory activity recorded from STN between ultradian sleep states to determine whether sleep-stage dependent spectral patterns might reflect underlying dysfunction. For this study, PD (n=10) subjects were assessed with concurrent polysomnography and LFP recordings from the DBS electrodes, for an average of 7.5 hours in ‘off’ dopaminergic medication state. Across subjects, we found conserved spectral patterns among the canonical frequency bands (delta 0–3 Hz, theta 3–7 Hz, alpha 7–13 Hz, beta 13–30 Hz, gamma 30–90 Hz and high frequency 90–350 Hz) that were associated with specific sleep cycles: delta (0–3 Hz) activity during non-rapid eye movement (NREM) associated stages was greater than during Awake, whereas beta (13–30 Hz) activity during NREM states was lower than Awake and rapid eye movement (REM). In addition, all frequency bands were significantly different between NREM states and REM. However, each individual subject exhibited a unique mosaic of spectral interrelationships between frequency bands. Our work suggests that LFP recordings from human STN differentiate between sleep cycle states, and sleep-state specific spectral mosaics may provide insight into mechanisms underlying sleep pathophysiology.

Introduction The P50, a positive auditory-evoked potential occurring 50 msec after an auditory click, has been characterized extensively with electroencephalography (EEG) to detect aberrant auditory electrophysiology in disorders like schizophrenia (SZ) where 61-74% have an auditory gating deficit. The P50 response occurs in primary auditory cortex and several thalamocortical regions. In rodents, the gated P50 response has been identified in the reticular thalamic nucleus (RT)-a deep brain structure traversed during deep brain stimulation (DBS) targeting of the ventral intermediate nucleus (VIM) of the thalamus to treat essential tremor (ET) allowing for interspecies comparison. The goal was to utilize the unique opportunity provided by DBS surgery for ET to map the P50 response in multiple deep brain structures in order to determine the utility of intraoperative P50 detection for facilitating DBS targeting of auditory responsive subterritories. Materials and methods We developed a method to assess P50 response intraoperatively with local field potentials (LFP) using microelectrode recording during routine clinical electrophysiologic mapping for awake DBS surgery in seven ET patients. Recording sites were mapped into a common stereotactic space. Results Forty significant P50 responses of 155 recordings mapped to the ventral thalamus, RT and CN head/body interface at similar rates of 22.7-26.7%. P50 response exhibited anatomic specificity based on distinct positions of centroids of positive and negative responses within brain regions and the fact that P50 response was not identified in the recordings from either the internal capsule or the dorsal thalamus. Conclusions Detection of P50 response intraoperatively may guide DBS targeting RT and subterritories within CN head/body interface-DBS targets with the potential to treat psychosis and shown to modulate schizophrenia-like aberrancies in mouse models.

Background and purpose MR-guided laser interstitial thermal therapy (MRgLITT) is an increasingly popular neuroablative method for the surgical treatment of epilepsy patients. This article intends to demonstrate the utility and pitfalls of imaging in the context of patient care with MRgLITT. Material and methods A retrospective review of the medical records and imaging database with six illustrative cases selected to demonstrate the use of imaging throughout patient management with MRgLITT in diverse clinical situations and pathologies. A review of the knowledge in the literature was applied to the relevant points discussed. Results Imaging findings were described in the setting of laser therapy in nonlesional epilepsy, mesial temporal sclerosis, dual pathology, periventricular nodular heterotopia, and schizencephaly. Discussion of imaging principles, potential pitfalls, as well as its use in the patient work-up and follow-up, is shown. Conclusions MRgLITT is an alternative minimally invasive therapy for refractory epilepsy, which is becoming widely sought for. Imaging plays a crucial role prior to, during, and after the procedure.

Objective: The success of deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) depends on accurately placing the electrode into the GPi motor territory. Direct targeting can be difficult as GPi laminar borders are not always clearly identifiable on MRI. Here, we report a method for using the putamen (PUT) as a surrogate anatomical marker to target the GPi. Methods: We developed a PUT-based GPi targeting using the FGATIR (fast gray matter acquisition T1-weighted inversion recovery) MRI sequence and compared it with consensus coordinate-based indirect targeting. Stereotactic target coordinates were obtained and analyzed. Results: In our GPi DBS case sequences, GPi borders were unresolvable on T2-weighted MRI. However, in all cases, application of the PUT-based method resulted in consistently localized GPi targets, which were confirmed by merging the T2-weighted MRI with the FGATIR MRI. Significant differences were noted in the target coordinates between the PUT-based method and indirect targeting based on both the distance from the anterior commissure and the distance from the intercommissural plane. The mean differences for mediolateral distance and anteroposterior distance were 1.4 and 1.42 mm, respectively. In addition, the PUT-based method estimated a target that was closer to the nearest implanted electrode. Conclusion: Our PUT-based method allows consistent and precise patient-specific GPi targeting. Further study is planned to correlate PUT-based GPi targeting with microelectrode recording, location of active contact of the DBS electrode and clinical outcome.

Background/Aims: Laser interstitial thermal therapy (LITT) has become an alternative to open-resective surgery for refractory mesial temporal lobe epilepsy (MTLE). Occurrence of visual field defects (VFDs) following open surgery for MTLE is reported at 52-100%. We examined the rate of VFDs following LITT for amygdalohippocampectomy (AHE) and correlated the occurrence of VFDs with damage to the optic radiations, assessed by diffusion tensor tractography (DTI). Methods: We performed a retrospective analysis of 5 patients who underwent LITT-AHE for medically refractory MTLE. We examined the association between VFDs and optic radiation damage by correlating postprocedural visual field testing with qualitative assessment of optic radiation fiber tracts. Results: Postoperative assessments showed that 4 patients had normal visual field testing, and 1 had a right superior quadrantanopsia (20%). We performed 3-dimensional reconstruction of the optic radiation, laser probe trajectory, and ablation volume. Damage to Meyer's loop was determined consistent with the VFD. Conclusions: Short-term follow-up in our series suggests that laser ablation AHE may be associated with a lower rate of VFD than has been reported for open AHE. Our results suggest that incorporating optic radiation mapping through DTI may preoperatively help to minimize the risk of VFD following laser ablation AHE.

Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by complex recapitulations of waking acts during REM sleep due to unsuppressed voluntary muscle tone. Long-term studies indicate that RBD strongly predicts the subsequent development of Parkinson's disease (PD), Lewy body disease, and multiple system atrophy, with a conversion rate approaching 80%. Localizing the aberrant circuits involved in RBD has focused on the networks associated with REM generation, including the sublateral dorsal nucleus, the mesopontine tegmentum, and the pedunculopontine tegmental nucleus—nuclei affected by circuit dysregulation in PD. Interestingly, parkinsonism transiently abates during RBD complex movements, suggesting that movement during RBD may bypass the circuitry affected in PD, including the basal ganglia. Only recently have electrophysiological recordings in PD during sleep informed our understanding of how abnormal activity in the basal ganglia contributes to sleep dysregulation, specifically to RBD. Here, we highlight the pathophysiology shared between RBD and PD, focusing on the presumed aberrant neural networks, based on neuroimaging and neurophysiology data collected from human RBD and PD populations.

OBJECTIVE Cross-frequency coupling has been reported in the STN of patients with PD, but its significance and functional role are still not well understood. This study investigates pharmacological modulations of subthalamic oscillations and their nonlinear cross-frequency interactions across three consecutive cycles over unique 24-hour-long recordings. BACKGROUND Identifying neurobiomarkers for PD can drive the development of novel personalized treatments by providing objective assessment of impairment. In particular, distinct frequency bands in LFP recordings and their interaction with one another have been shown to modulate with dopaminergic medication and thus, proposed as such biomarkers. METHODS We recorded local field potentials 3 weeks postoperatively from externalized leads in 9 patients and correlated the neural patterns with improvements in motor signs over three medication intake cycles. We used two modalities to assess symptoms in the unmedicated OFF and the l-dopa-induced motor ON state: a subsection of the UPDRS and a keyboard tapping score measuring bradykinesia. RESULTS In the OFF state, the amplitude of high-frequency oscillations in the 200- to 300-Hz range was coupled with the phase of low-beta (13-22 Hz) in all patients. After transition to the ON state, three distinct coupling patterns were observed among subjects. Among these, patients showing ON coupling between high-beta (22-30 Hz) and high-frequency oscillations in the 300- to 400-Hz range had significantly greater improvement in bradykinesia, according to the keyboard scores. CONCLUSION Observing diminished coupling in the ON state, previous studies have hypothesized that the sole existence of coupling in STN has an "impeding" effect on normal processes, and thus it was considered to be pathological. In contrast, our observation of ON state coupling at distinct frequencies associated with the improvements in motor features suggest that the underlying mechanism of coupling might have impeding or enhancing effects depending on the coupled frequencies. © 2019 International Parkinson and Movement Disorder Society.

Although motor subtypes of Parkinson's disease (PD), such as tremor dominant (TD) and postural instability and gait difficulty (PIGD), have been defined based on symptoms since the mid-1990s, no underlying neural correlates of these clinical subtypes have yet been identified. Very limited data exist regarding the electrophysiological abnormalities within the subthalamic nucleus (STN) that likely accompany the symptom severity or the phenotype of PD. Here, we show that activity in subbands of local field potentials (LFPs) recorded with multiple microelectrodes from subterritories of STN provide distinguishing neurophysiological information about the motor subtypes of PD. We studied 24 patients with PD and found distinct patterns between TD (n = 13) and PIGD (n = 11) groups in high-frequency oscillations (HFOs) and their nonlinear interactions with beta band in the superior and inferior regions of the STN. Particularly, in the superior region of STN, the power of the slow HFO (sHFO) (200-260 Hz) and the coupling of its amplitude with beta-band phase were significantly stronger in the TD group. The inferior region of STN exhibited fast HFOs (fHFOs) (260-450 Hz), which have a significantly higher center frequency in the PIGD group. The cross-frequency coupling between fHFOs and beta band in the inferior region of STN was significantly stronger in the PIGD group. Our results indicate that the spatiospectral dynamics of STN-LFPs can be used as an objective method to distinguish these two motor subtypes of PD. These observations might lead to the development of sensing and stimulation strategies targeting the subterritories of STN for the personalization of deep-brain stimulation (DBS).

Background:Epilepsy surgery (ES) can improve seizure outcome. A prolonged duration of presurgical evaluation contributes to epilepsy-related morbidity and mortality. We introduced process changes to decrease evaluation time (ET) and increase ES numbers (excluding vagus nerve stimulation).Methods:The University of Colorado Hospital patient database was searched for ESs between January 2009 and May 2016. Measures to reduce ET included (1) increasing patient care conference (PCC) frequency; (2) faster intracarotid amobarbital test (IAT) scheduling; (3) dedicated ES clinic; and (4) adding a nurse navigator. ET from noninvasive video-EEG monitoring (P1) to IAT, PCC, and ES, and ES volume were determined and compared for a baseline group (P1 January 2009–March 2013) and a group exposed to process changes (P1 after March 2013), the postchanges group, to assess the effect of these measures.Results:ES number was 61 for the baseline group and 77 for the postchanges group, increasing the annual rate at 3 years after changes from 14.4 to 36.8 (p = 0.0008; 37% yearly increase postchanges). Interventions lowered average ET by 96 days (p ≤ 0.0001), P1 to IAT by 39 days (p = 0.0011), and P1 to PCC by 58 days (p = 0.0002).Conclusions:Simple process changes, including more frequent patient care conferences, faster scheduling, a dedicated ES clinic, and a nurse navigator significantly decreased evaluation times and increased ES numbers. Centers could utilize similar strategies to improve process and surgical volume and thereby increase patient seizure control and safety.

Question 1 Is bilateral subthalamic nucleus deep brain stimulation (STN DBS) more, less, or as effective as bilateral globus pallidus internus deep brain stimulation (GPi DBS) in treating motor symptoms of Parkinson's disease, as measured by improvements in Unified Parkinson's Disease Rating Scale, part III (UPDRS-III) scores? Recommendation Given that bilateral STN DBS is at least as effective as bilateral GPi DBS in treating motor symptoms of Parkinson's disease (as measured by improvements in UPDRS-III scores), consideration can be given to the selection of either target in patients undergoing surgery to treat motor symptoms. (Level I). Question 2 Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in allowing reduction of dopaminergic medication in Parkinson's disease? Recommendation When the main goal of surgery is reduction of dopaminergic medications in a patient with Parkinson's disease, then bilateral STN DBS should be performed instead of GPi DBS. (Level I). Question 3 Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in treating dyskinesias associated with Parkinson's disease? Recommendation There is insufficient evidence to make a generalizable recommendation regarding the target selection for reduction of dyskinesias. However, when the reduction of medication is not anticipated and there is a goal to reduce the severity of "on" medication dyskinesias, the GPi should be targeted. (Level I). Question 4 Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in improving quality of life measures in Parkinson's disease? Recommendation When considering improvements in quality of life in a patient undergoing DBS for Parkinson's disease, there is no basis to recommend bilateral DBS in 1 target over the other. (Level I). Question 5 Is bilateral STN DBS associated with greater, lesser, or a similar impact on neurocognitive function than bilateral GPi DBS in Parkinson disease? Recommendation If there is significant concern about cognitive decline, particularly in regards to processing speed and working memory in a patient undergoing DBS, then the clinician should consider using GPi DBS rather than STN DBS, while taking into consideration other goals of surgery. (Level I). Question 6 Is bilateral STN DBS associated with a higher, lower, or similar risk of mood disturbance than GPi DBS in Parkinson's disease? Recommendation If there is significant concern about the risk of depression in a patient undergoing DBS, then the clinician should consider using pallidal rather than STN stimulation, while taking into consideration other goals of surgery. (Level I). Question 7 Is bilateral STN DBS associated with a higher, lower, or similar risk of adverse events compared to GPi DBS in Parkinson's disease? Recommendation There is insufficient evidence to recommend bilateral DBS in 1 target over the other in order to minimize the risk of surgical adverse events. The full guideline can be found at: https://www.cns.org/guidelines/deep-brain-stimulation-parkinsons-disease.

Metastatic melanoma appears to have inferior local control (LC) than renal cell carcinoma (RCC) after stereotactic radiosurgery (SRS) to the brain.To retrospectively examine RCC vs. melanoma LC dose response.Follow-up data were available for 88 patients (RCC=38; melanoma=50) with 235 tumors (RCC=92; melanoma=143) treated with Gamma Knife SRS between Dec. 2005 to Aug. 2012. LC was compared among RCC vs. melanoma and then at each margin dose (≤18Gy, 20Gy, 22Gy, and 24Gy). Patient survival and toxicity were analyzed. Median follow-up was 9.8 months (RCC) and 5.4 months (melanoma).Patient characteristics were similar between RCC vs. melanoma with respect to gender, age, KPS, GPA, lesions per patient, and tumor volume. For all margin doses, LC at 6 months was 98.6% (RCC) vs. 79.2% (melanoma). When broken down by margin dose, at ≤18 Gy (P0.0001) and 20 Gy (P=0.02), RCC had better LC compared to melanoma. At 22 Gy, LC were similar between the two histologies (P=0.19). At 24 Gy, melanoma had better LC than RCC (P=0.02). Tumor volumes were similar between RCC vs. melanoma at each margin dose (P0.05). Small melanoma tumors (4ml) exhibited LC dose dependence. Median survival was 16.1 months (RCC) and 9.6 months (melanoma). Toxicity was not significantly different between the two histologies and margin doses.RCC has significantly better LC than melanoma after SRS. Higher doses could be used for melanoma tumors4ml to improve melanoma LC.

Learning surgical skills is the main task for neurosurgery residency training, in which technical errors may result in poor or even devastating consequences. Recently simulation technology has been developed as adjunctive means for neurosurgical training and may provide residents with abilities to acquire surgical skills in a safe environment. Magnetic resonance-guided laser interstitial thermal therapy has been shown to be a minimally invasive and effective alternative treatment for selected patients with mesial temporal lobe epilepsy. However, high levels of functioning in the patients with temporal lobe epilepsy and esoteric interventions of laser ablation procedures performed in fewer medical centers have prevented hands-on training for surgeons. Moreover, working-hour restrictions of neurosurgery residency makes it necessary to deliver high-quality and time-effective training to surgeons in less time while ensuring optimal patient outcomes. This chapter focuses on the simulation of laser ablation amygdalo-hippocampectomy for treatment of mesial temporal lobe epilepsy.

OBJECTIVEDeep brain stimulation (DBS) of the subthalamic nucleus (STN) has become standard care for the surgical treatment of Parkinson’s disease (PD). Reliable interpretation of microelectrode recording (MER) data, used to guide DBS implantation surgery, requires expert electrophysiological evaluation. Recent efforts have endeavored to use electrophysiological signals for automatic detection of relevant brain structures and optimal implant target location.The authors conducted an observational case-control study to evaluate a software package implemented on an electrophysiological recording system to provide online objective estimates for entry into and exit from the STN. In addition, they evaluated the accuracy of the software in selecting electrode track and depth for DBS implantation into STN, which relied on detecting changes in spectrum activity.METHODSData were retrospectively collected from 105 MER-guided STN-DBS surgeries (4 experienced neurosurgeons; 3 sites), in which estimates for entry into and exit from the STN, DBS track selection, and implant depth were compared post hoc between those determined by the software and those determined by the implanting neurosurgeon/neurophysiologist during surgery.RESULTSThis multicenter study revealed submillimetric agreement between surgeon/neurophysiologist and software for entry into and exit out of the STN as well as optimal DBS implant depth.CONCLUSIONSThe results of this study demonstrate that the software can reliably and accurately estimate entry into and exit from the STN and select the track corresponding to ultimate DBS implantation.

Based on the success of deep brain stimulation (DBS) for treating movement disorders, there is growing interest in using DBS to treat schizophrenia (SZ). We review the unmet needs of patients with SZ and the scientific rationale behind the DBS targets proposed in the literature in order to guide future development of DBS to treat this vulnerable patient population. SZ remains a devastating disorder despite treatment. Relapse, untreated psychosis, intolerable side effects and the lack of effective treatment for negative and cognitive symptoms contribute to poor outcome. Novel therapeutic interventions are needed to treat SZ and DBS is emerging as a potential intervention. Convergent genetic, pharmacological and neuroimaging evidence implicating neuropathology associated with psychosis is consistent with SZ being a circuit disorder amenable to striatal modulation with DBS. Many of the DBS targets proposed in the literature may modulate striatal dysregulation. Additional targets are considered for treating tardive dyskinesia and negative and cognitive symptoms. A need is identified for the concurrent development of neurophysiological biomarkers relevant to SZ pathology in order to inform DBS targeting. Finally, we discuss the current clinical trials of DBS for SZ, and their ethical considerations. We conclude that patients with severe symptoms despite treatment must have the capacity to consent for a DBS clinical trial in which risks can be estimated, but benefit is not known. In addition, psychiatric populations should have access to the potential benefits of neurosurgical advances.

Epilepsy is a common neurological disorder occurring in 3% of the US adult population. It is characterised by seizures resulting from aberrant hypersynchronous neural activity. Approximately one-third of newly diagnosed epilepsy cases fail to become seizure-free in response to antiseizure drugs. Optimal seizure control, in cases of drug-resistant epilepsy, often requires neurosurgical intervention targeting seizure foci, such as the temporal lobe. Advances in minimally invasive ablative surgical approaches have led to the development of MRI-guided laser interstitial thermal therapy (LITT). For refractory epilepsy, this surgical intervention offers many advantages over traditional approaches, including real-time lesion monitoring, reduced morbidity, and in some reports increased preservation of cognitive and language processes. We review the use of LITT for epileptic indications in the context of its application as a curative (seizure freedom) or palliative (seizure reduction) measure for both lesional and non-lesional forms of epilepsy. Furthermore, we address the use of LITT for a variety of extratemporal lobe epilepsies. Finally, we describe clinical outcomes, limitations and future applications of LITT for epilepsy.

Identification of brain structures traversed during implantation of deep brain‐stimulating (DBS) electrodes into the subthalamic nucleus (STN‐DBS) for the treatment of Parkinson's disease (PD) frequently relies on subjective correspondence between kinesthetic response and multiunit activity. However, recent work suggests that local field potentials (LFP) could be used as a more robust signal to objectively differentiate subcortical structures. The goal of this study was to analyze the spectral properties of LFP collected during STN‐DBS in order to objectively identify commonly traversed brain regions and improve our understanding of aberrant oscillations in the PD‐related pathophysiological cortico‐basal ganglia network. In 21 PD patients, LFP were collected and analyzed during STN‐DBS implantation surgery. Spectral power for delta‐, theta‐, alpha‐, low‐beta‐, and high‐beta‐frequency bands was assessed at multiple depths throughout the subcortical structures traversed on the trajectory to the ventral border of STN. Similar to previous findings, beta‐band oscillations had an increased magnitude within the borders of the motor‐related area of STN, however, across several subjects, we also observed increased high‐beta magnitude within the borders of thalamus. Comparing across all patients using relative power, we observed a gradual increase in the magnitude of both low‐ and high‐beta‐frequency bands as the electrode descended from striatum to STN. These results were also compared with frequency bands below beta, and similar trends were observed. Our results suggest that LFP signals recorded during the implantation of a DBS electrode evince distinct oscillatory signatures that distinguish subcortical structures.

OBJECTIVES/SPECIFIC AIMS: The goal for this project is to determine the feasibility of using a novel multi-photon fiber-coupled microscope to aid surgeons in localizing STN during surgeries. In order to accomplish this goal, we needed to identify the source of a strong autofluorescent signal in the STN and determine whether we could use image classification methods to automatically distinguish STN from surrounding brain regions. METHODS/STUDY POPULATION: We acquired 3 cadaveric brains from the University of Colorado Anschutz Medical Campus, Department of Pathology. Two of these brains were non-PD controls whereas 1 was diagnosed with PD. We dissected a 10 square centimeter region of midbrain surrounding STN, then prepared this tissue for slicing on a vibratome or cryostat. Samples were immuno-labeled for various cellular markers for identification, or left unlabeled in order to observe the autofluorescence for image classification. RESULTS/ANTICIPATED RESULTS: The border of STN is clearly visible based on the density of a strong autofluorescent signal. The autofluorescent signal is visible using 2-photon (850–1040 nm excitation) and conventional confocal microscopy (488–647 nm excitation). We were also able to visualize blood vessels with second harmonic generation. The autofluorescent signal is quenched by high concentrations of Sudan-black B (0.5%–5%), and is primarily localized in microtubule-associated protein-2 (MAP2)+ cells, indicating that it is likely lipofuscin accumulation in neurons. Smaller lipofuscin particles also accumulate in microglia, identified based on ionized calcium binding adopter 1 (Iba1)+ labeling. We anticipate that colocalization analysis will confirm these qualitative observations. Using 2-photon images of the endogenous autofluorescent signal in these samples, we trained a logistic regression-based image classifier using features derived from gray-level co-occurrence matrices. Preliminary testing indicates that our classifier performed well, with a mean accuracy of 0.89 (standard deviation of 0.11) and a Cohen’s Kappa value of 0.76 (standard deviation of 0.24). We are currently using coherent anti-Stokes Raman scattering and third harmonic imaging to identify different features of myelin that can be used to distinguish between these regions and expect similar results. DISCUSSION/SIGNIFICANCE OF IMPACT: Traditional methods for localizing STN during DBS surgery include the use of stereotactic coordinates and multi-electrode recording (MER) during implantation. MERs are incredibly useful in DBS surgeries, but require penetration of brain structures in order to infer location. Using multi-photon microscopy techniques to aid identification of STN during DBS surgeries offers a number of advantages over traditional methods. For example, blood vessels can be clearly identified with second harmonic generation, something that is not possible with MER. Multi-photon microscopy also allows visualization deep into tissue without actually penetrating it. This ability to look within a depth of field is useful for detection of STN borders based on autofluorescent cell density. When combined with traditional stereotactic information, our preliminary image classification methods are a fast, reliable way to provide surgeons with extra information concerning their location in the midbrain. We anticipate that future advancements and refinements to our image classifier will only increase accuracy and the potential applications and value. In summary, these preliminary data support the feasibility of multi-photon microscopy to aid in the identification of target brain regions during DBS surgeries. The techniques described here complement and enhance current stereotactic and electrophysiological methods for DBS surgeries.

This workshop addressed challenges of clinical research in neurosurgery. Randomized controlled clinical trials (RCTs) have high internal validity, but often insufficiently generalize to real-world practice. Observational studies are inclusive but often lack sufficient rigor. The workshop considered possible solutions, such as (1) statistical methods for demonstrating causality using observational data; (2) characteristics required of a registry supporting effectiveness research; (3) trial designs combining advantages of observational studies and RCTs; and (4) equipoise, an identified challenge for RCTs. In the future, advances in information technology potentially could lead to creation of a massive database where clinical data from all neurosurgeons are integrated and analyzed, ending the separation of clinical research and practice and leading to a new "science of practice."

Overall Abstract: Schizophrenia is a common and severe neuropsychiatric disorder of unknown etiology. Dorsolateral prefrontal cortex (DLPFC) and its connection through mediodorsal thalamus have been implicated in decreased cortical dopamine and schizophrenia pathology. Negative symptoms, such as social withdrawal and general lack of motivation and engagement, are prominent in 20%–40% of patients with schizophrenia and have been attributed to aberrancies in the reward system of the ventral striatum via lowering of dopaminergic tone in nucleus accumbens (NAc). Some success has been reported in alleviating negative symptoms of schizophrenia through high-frequency repetitive magnetic stimulation of the left DLPFC. Case reports provide support for capsulotomy and deep brain stimulation of NAc in the treatment of psychosis, in the reduction of negative symptoms, and in improvement of motivation. Converging evidence supporting the targeting of NAc with reversible, modifiable deep brain stimulation, to modulate cortico-striatal-thalamo-cortical circuitry, and thereby treat symptoms of schizophrenia, will be discussed.

MR-guided laser interstitial thermal therapy (MRgLITT) is an increasingly popular neuroablative method for the surgical treatment of epilepsy patients. This article intends to demonstrate the utility and pitfalls of imaging in the context of patient care with MRgLITT.A retrospective review of the medical records and imaging database with six illustrative cases selected to demonstrate the use of imaging throughout patient management with MRgLITT in diverse clinical situations and pathologies. A review of the knowledge in the literature was applied to the relevant points discussed.Imaging findings were described in the setting of laser therapy in nonlesional epilepsy, mesial temporal sclerosis, dual pathology, periventricular nodular heterotopia, and schizencephaly. Discussion of imaging principles, potential pitfalls, as well as its use in the patient work-up and follow-up, is shown.MRgLITT is an alternative minimally invasive therapy for refractory epilepsy, which is becoming widely sought for. Imaging plays a crucial role prior to, during, and after the procedure.

Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterised by complex motor enactment of dreams and is a potential prodromal marker of Parkinson9s disease (PD). Of note, patients with PD observed during RBD episodes exhibit improved motor function, relative to baseline states during wake periods. Here, we review recent epidemiological and mechanistic findings supporting the prodromal value of RBD for PD, incorporating clinical and electrophysiological studies. Explanations for the improved motor function during RBD episodes are evaluated in light of recent publications. In addition, we present preliminary findings describing changes in the activity of the basal ganglia across the sleep–wake cycle that contribute to our understanding of RBD.