Neuromodulation: What the neurointerventionalist needs to know.

Neuromodulation is the alteration of neural activity in the central, peripheral, or autonomic nervous systems. Consequently, this term lends itself to a variety of organ systems including but not limited to the cardiac, nervous, and even gastrointestinal systems. In this review, we provide a primer on neuromodulation, examining the various technological systems employed and neurological disorders targeted with this technology. Ultimately, we undergo a historical analysis of the field's development, pivotal discoveries and inventions gearing this review to neuro-adjacent subspecialties with a specific focus on neurointerventionalists.

Electroencephalography as a tool to predict cerebral oxygen metabolism during deep-hypothermic circulatory arrest in neonates with critical congenital heart disease.

Objectives: Recent research suggests that increased cerebral oxygen use during surgical intervention for neonates with congenital heart disease may play a role in the development of postoperative white matter injury. The objective of this study is to determine whether increased cerebral electrical activity correlates with greater decrease of cerebral oxygen saturation during deep hypothermic circulatory arrest. Methods: Neonates with critical congenital heart disease requiring surgical intervention during the first week of life were studied. All subjects had continuous neuromonitoring with electroencephalography and an optical probe (to quantify cerebral oxygen saturation) during cardiac surgical repair that involved the use of cardiopulmonary bypass and deep hypothermic circulatory arrest. A simple linear regression was used to investigate the association between electroencephalography metrics before the deep hypothermic circulatory arrest period and the change in cerebral oxygen saturation during the deep hypothermic circulatory arrest period. Results: Sixteen neonates had both neuromonitoring modalities attached during surgical repair. Cerebral oxygen saturation data from 5 subjects were excluded due to poor data quality, yielding a total sample of 11 neonates. A simple linear regression model found that the presence of electroencephalography activity at the end of cooling is positively associated with the decrease in cerebral oxygen saturation that occurs during deep hypothermic circulatory arrest (P < .05). Conclusions: Electroencephalography characteristics within 5 minutes before the initiation of deep hypothermic circulatory arrest may be useful in predicting the decrease in cerebral oxygen saturation that occurs during deep hypothermic circulatory arrest. Electroencephalography may be an important tool for guiding cooling and the initiation of circulatory arrest to potentially decrease the prevalence of new white matter injury in neonates with critical congenital heart disease.

Gamma Knife radiosurgery for trigeminal neuralgia provides greater pain relief at higher dose rates.

In Gamma Knife (GK) radiosurgery, dose rate decreases during the life cycle of its radiation source, extending treatment times. Prolonged treatments influence the amount of sublethal radiation injury that is repaired during exposure, and is associated with decreased biologically-equivalent dose (BED). We assessed the impact of treatment times on clinical outcomes following GK of the trigeminal nerve - a rare clinical model to isolate the effects of treatment times. This is a retrospective analysis of 192 patients with facial pain treated across three source exchanges. All patients were treated to 80 Gy with a single isocenter. Treatment time was analyzed in terms of patient anatomy-specific dose rate, as well as BED calculated from individual patient beam-on times. An outcome tool measuring pain in three distinct domains (pain intensity, interference with general and oro-facial activities of daily living), was administered before and after intervention. Multivariate linear regression was performed with dose rate/BED, brainstem dose, sex, age, diagnosis, and prior intervention as predictors. BED was an independent predictor of the degree of improvement in all three dimensions of pain severity. A decrease in dose rate by 1.5 Gy/min corresponded to 31.8% less improvement in the overall severity of pain. Post-radiosurgery incidence of facial numbness was increased for BEDs in the highest quartile. Treatment time is an independent predictor of pain outcomes, suggesting that prescription dose should be customized to ensure iso-effective treatments, while accounting for the possible increase in adverse effects at the highest BEDs.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor Under General Anesthesia: Technical Note.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an incisionless therapy for the treatment of medication-resistant essential tremor. Although its safety and efficacy has been demonstrated, MRgFUS is typically performed with the patient awake, with intraprocedural neurological assessments to guide lesioning. OBJECTIVE: To report the first case of MRgFUS thalamotomy under general anesthesia in a patient whose medical comorbidities prohibit him from being in a supine position without a secured airway. METHODS: The dentatorubrothalamic tract was directly targeted. Two sonications reaching lesional temperatures (≥54°C) were delivered without any complications. RESULTS: Lesioning was confirmed on intraoperative magnetic resonance imaging, and the patient experienced 89% improvement in his tremor postoperatively. CONCLUSION: This demonstrates the safety and feasibility of MRgFUS thalamotomy under general anesthesia without the benefit of intraprocedural neurological assessments.

Effects of circulatory arrest and cardiopulmonary bypass on cerebral autoregulation in neonatal swine.

BACKGROUND: Cerebral autoregulation mechanisms help maintain adequate cerebral blood flow (CBF) despite changes in cerebral perfusion pressure. Impairment of cerebral autoregulation, during and after cardiopulmonary bypass (CPB), may increase risk of neurologic injury in neonates undergoing surgery. In this study, alterations of cerebral autoregulation were assessed in a neonatal swine model probing four perfusion strategies. METHODS: Neonatal swine (n = 25) were randomized to continuous deep hypothermic cardiopulmonary bypass (DH-CPB, n = 7), deep hypothermic circulatory arrest (DHCA, n = 7), selective cerebral perfusion (SCP, n = 7) at deep hypothermia, or normothermic cardiopulmonary bypass (control, n = 4). The correlation coefficient (LDx) between laser Doppler measurements of CBF and mean arterial blood pressure was computed at initiation and conclusion of CPB. Alterations in cerebral autoregulation were assessed by the change between initial and final LDx measurements. RESULTS: Cerebral autoregulation became more impaired (LDx increased) in piglets that underwent DH-CPB (initial LDx: median 0.15, IQR [0.03, 0.26]; final: 0.45, [0.27, 0.74]; p = 0.02). LDx was not altered in those undergoing DHCA (p > 0.99) or SCP (p = 0.13). These differences were not explained by other risk factors. CONCLUSIONS: In a validated swine model of cardiac surgery, DH-CPB had a significant effect on cerebral autoregulation, whereas DHCA and SCP did not. IMPACT: Approximately half of the patients who survive neonatal heart surgery with cardiopulmonary bypass (CPB) experience neurodevelopmental delays. This preclinical investigation takes steps to elucidate and isolate potential perioperative risk factors of neurologic injury, such as impairment of cerebral autoregulation, associated with cardiac surgical procedures involving CPB. We demonstrate a method to characterize cerebral autoregulation during CPB pump flow changes in a neonatal swine model of cardiac surgery. Cerebral autoregulation was not altered in piglets that underwent deep hypothermic circulatory arrest (DHCA) or selective cerebral perfusion (SCP), but it was altered in piglets that underwent deep hypothermic CBP.

Development of an Intraoperative Pipeline for Holographic Mixed Reality Visualization During Spinal Fusion Surgery.

Objective. Holographic mixed reality (HMR) allows for the superimposition of computer-generated virtual objects onto the operator's view of the world. Innovative solutions can be developed to enable the use of this technology during surgery. The authors developed and iteratively optimized a pipeline to construct, visualize, and register intraoperative holographic models of patient landmarks during spinal fusion surgery. Methods. The study was carried out in two phases. In phase 1, the custom intraoperative pipeline to generate patient-specific holographic models was developed over 7 patients. In phase 2, registration accuracy was optimized iteratively for 6 patients in a real-time operative setting. Results. In phase 1, an intraoperative pipeline was successfully employed to generate and deploy patient-specific holographic models. In phase 2, the registration error with the native hand-gesture registration was 20.2 ± 10.8 mm (n = 7 test points). Custom controller-based registration significantly reduced the mean registration error to 4.18 ± 2.83 mm (n = 24 test points, P < .01). Accuracy improved over time (B = -.69, P < .0001) with the final patient achieving a registration error of 2.30 ± .58 mm. Across both phases, the average model generation time was 18.0 ± 6.1 minutes (n = 6) for isolated spinal hardware and 33.8 ± 8.6 minutes (n = 6) for spinal anatomy. Conclusions. A custom pipeline is described for the generation of intraoperative 3D holographic models during spine surgery. Registration accuracy dramatically improved with iterative optimization of the pipeline and technique. While significant improvements and advancements need to be made to enable clinical utility, HMR demonstrates significant potential as the next frontier of intraoperative visualization.

Inequalities in Meningioma Survival: Results from the National Cancer Database.

Background Meningiomas are the second most common primary tumors of the central nervous system. However, there is a paucity of literature examining how healthcare, demographic, and socioeconomic factors impact patient outcomes. Methods We conducted a retrospective study of 65,812 patients from the National Cancer Database (NCDB; 2004-2012) who received treatment for their meningioma. Univariate and multivariate analyses were performed with the overall five-year survival as the primary outcome, and the following factors: facility type, geography, housing area, patient insurance, sex, ethnicity, race, income, and education. The multivariate model was adjusted for patient age, co-morbidity, tumor size, behavior, and treatment strategy. Results Diagnosis and treatment at an academic/research program, private insurance, female sex, Hispanic ethnicity, and high school diploma conferred a survival advantage on both univariate and multivariate analyses. Conclusions Disparities in survival outcomes in patients with meningiomas exist across multiple healthcare, demographic, and socioeconomic factors. Additional research is needed to elucidate the genetic and environmental factors driving these inequalities.

Electroencephalographic Response to Deep Hypothermic Circulatory Arrest in Neonatal Swine and Humans.

BACKGROUND: Piglets are used to study neurologic effects of deep hypothermic circulatory arrest (DHCA), but no studies have compared human and swine electroencephalogram (EEG) responses to DHCA. The importance of isoelectricity before circulatory arrest is not fully known in neonates. We compared the EEG response to DHCA in human neonates and piglets. METHODS: We recorded 2 channel, left and right centroparietal, subdermal EEG in 10 neonatal patients undergoing operations involving DHCA and 10 neonatal piglets that were placed on cardiopulmonary bypass and underwent a simulated procedure using DHCA. EEG waveforms were analyzed for the presence and extent of burst suppression and isoelectricity by automated moving window analysis. The patients were monitored with 16-channel array EEG for 48 hours postoperatively and underwent postoperative brain magnetic resonance imaging. RESULTS: After induction of anesthesia, humans and piglets both displayed slowing or brief suppression, then mild burst suppression, and then severe burst suppression during cooling. All piglets subsequently achieved isoelectricity at 22.4° ± 6.9°C, whereas only 1 human did at 20.2°C. Piglets and humans emerged from severe, mild, and then brief suppression patterns during rewarming. Among the patients, there were no seizures during postoperative monitoring and 1 instance of increased white matter injury on postoperative magnetic resonance imaging. CONCLUSIONS: Our data suggest that current cooling strategies may not be sufficient to eliminate all EEG activity before circulatory arrest in humans but are sufficient in swine. This important difference between the swine and human response to DHCA should be considered when using this model.

Cerebral mitochondrial dysfunction associated with deep hypothermic circulatory arrest in neonatal swine.

OBJECTIVES: Controversy remains regarding the use of deep hypothermic circulatory arrest (DHCA) in neonatal cardiac surgery. Alterations in cerebral mitochondrial bioenergetics are thought to contribute to ischaemia-reperfusion injury in DHCA. The purpose of this study was to compare cerebral mitochondrial bioenergetics for DHCA with deep hypothermic continuous perfusion using a neonatal swine model. METHODS: Twenty-four piglets (mean weight 3.8 kg) were placed on cardiopulmonary bypass (CPB): 10 underwent 40-min DHCA, following cooling to 18°C, 10 underwent 40 min DHCA and 10 remained at deep hypothermia for 40 min; animals were subsequently rewarmed to normothermia. 4 remained on normothermic CPB throughout. Fresh brain tissue was harvested while on CPB and assessed for mitochondrial respiration and reactive oxygen species generation. Cerebral microdialysis samples were collected throughout the analysis. RESULTS: DHCA animals had significantly decreased mitochondrial complex I respiration, maximal oxidative phosphorylation, respiratory control ratio and significantly increased mitochondrial reactive oxygen species (P < 0.05 for all). DHCA animals also had significantly increased cerebral microdialysis indicators of cerebral ischaemia (lactate/pyruvate ratio) and neuronal death (glycerol) during and after rewarming. CONCLUSIONS: DHCA is associated with disruption of mitochondrial bioenergetics compared with deep hypothermic continuous perfusion. Preserving mitochondrial health may mitigate brain injury in cardiac surgical patients. Further studies are needed to better understand the mechanisms of neurological injury in neonatal cardiac surgery and correlate mitochondrial dysfunction with neurological outcomes.