Microelectrode Recording During Deep Brain Stimulation Does Not Consistently Represent Lead Trajectory.

BACKGROUND AND OBJECTIVES: Long-term outcomes in deep brain stimulation (DBS) depend on accuracy of lead placement. Microelectrode recording (MER) is a long-used adjunct to leverage neurophysiological information to confirm satisfactory trajectory of implanted electrodes. The goal of this study was to evaluate the consistency in which electrodes are placed in sampled microelectrode trajectories. METHODS: This is a retrospective study using intraoperative computed tomography to measure final electrode deviation from MER probe placement during the DBS insertion targeting subthalamic nucleus. Fifteen patients had 29 DBS leads placed using MER assistance. Radial distance between the probe and the lead were measured for each patient using intraoperative imaging. In addition, the preoperative target to final lead error was measured in 14 patients undergoing subthalamic nucleus implants without the use of MER and compared with the 15 patients in which MER was used as an adjunct. RESULTS: There was no significant difference in the mean radial target error (1.2 vs 1.0 mm, P = .156) when comparing the leads placed with or without MER assistance, respectively. The mean difference in final position of microelectrode compared with DBS lead was 0.9 ± 0.1 (range 0.4-2.0 mm). Of all MER-assisted electrodes placed, 44.8% (13) of electrode final positions radially deviated 1.0 mm or more from the MER probe. CONCLUSION: Electrode placement may deviate significantly from MER trajectories. Given the concern that physiological data may not be representative of the final electrode trajectory, surgeons should consider using intraoperative imaging or other adjunctive techniques during DBS to confirm accuracy and satisfactory trajectory of DBS leads.

linc-ADAIN, a human adipose lincRNA, regulates adipogenesis by modulating KLF5 and IL-8 mRNA stability.

Adipose tissue remodeling and dysfunction, characterized by elevated inflammation and insulin resistance, play a central role in obesity-related development of type 2 diabetes (T2D) and cardiovascular diseases. Long intergenic non-coding RNAs (lincRNAs) are important regulators of cellular functions. Here, we describe the functions of linc-ADAIN (adipose anti-inflammatory), an adipose lincRNA that is downregulated in white adipose tissue of obese humans. We demonstrate that linc-ADAIN knockdown (KD) increases KLF5 and interleukin-8 (IL-8) mRNA stability and translation by interacting with IGF2BP2. Upregulation of KLF5 and IL-8, via linc-ADAIN KD, leads to an enhanced adipogenic program and adipose tissue inflammation, mirroring the obese state, in vitro and in vivo. KD of linc-ADAIN in human adipose stromal cell (ASC) hTERT adipocytes implanted into mice increases adipocyte size and macrophage infiltration compared to implanted control adipocytes, mimicking hallmark features of obesity-induced adipose tissue remodeling. linc-ADAIN is an anti-inflammatory lincRNA that limits adipose tissue expansion and lipid storage.

Learning Curves during Implementation of Robotic Stereotactic Surgery.

INTRODUCTION: Adoption of robotic techniques is increasing for neurosurgical applications. Common cranial applications include stereoelectroencephalography (sEEG) and deep brain stimulation (DBS). For surgeons to implement robotic techniques in these procedures, realistic learning curves must be anticipated for surgeons to overcome the challenges of integrating new techniques into surgical workflow. One such way of quantifying learning curves in surgery is cumulative sum (CUSUM) analysis. METHODS: Here, the authors present retrospective review of stereotactic cases to perform a CUSUM analysis of operative time for robotic cases at a single institution performed by 2 surgeons. The authors demonstrate learning phase durations of 20 and 16 cases in DBS and sEEG, respectively. RESULTS: After plateauing of operative time, mastery phases started at cases 132 and 72 in DBS and sEEG. A total of 273 cases (188 DBS and 85 sEEG) were included in the study. The authors observed a learning plateau concordant with change of location of surgery after exiting the learning phase. CONCLUSION: This study demonstrates the learning curve of 2 stereotactic workflows when integrating robotics as well as being the first study to examine the robotic learning curve in DBS via CUSUM analysis. This work provides data on what surgeons may expect when integrating this technology into their practice for cranial applications.

ADAMTS7 Promotes Smooth Muscle Cell Foam Cell Expansion in Atherosclerosis.

Human genetic studies have repeatedly associated SNPs near the gene ADAMTS7 with atherosclerotic cardiovascular disease. Subsequent investigations in mice demonstrated that ADAMTS7 is proatherogenic, induced in response to vascular injury, and alters smooth muscle cell function. However, the mechanisms governing this function and its relationship to atherosclerosis remain unclear. Here, we report the first conditional Adamts7 transgenic mouse in which the gene can be conditionally overexpressed in smooth muscle cells, mimicking its induction in atherosclerosis. We observed that smooth muscle cell Adamts7 overexpression results in a 3.5-fold increase in peripheral atherosclerosis, coinciding with an expansion of smooth muscle foam cells. RNA sequencing of Adamts7 overexpressed primary smooth muscle cells revealed an upregulation in the expression of lipid uptake genes. Subsequent experiments in primary smooth muscle cells demonstrated that increased Spi1 and Cd36 expression leads to increased smooth muscle cell oxLDL uptake. To uncover ADAMTS7 expression in human disease, we have interrogated the largest scRNA-seq dataset of human carotid atherosclerosis. This analysis discovered that endothelial cells had the highest expression level of ADAMTS7 with lesser expression in smooth muscle cells, fibroblasts, and mast cells. Subsequent conditional knockout studies in smooth muscle cells surprisingly showed no change in atherosclerosis, suggesting redundant expression of this secreted factor in the vessel wall. Finally, mice overexpressing Adamts7 in endothelial cells also exhibit increased atherosclerosis, suggesting that multiple vascular cell types can contribute to ADAMTS7-mediated foam cell expansion. In summary, Adamts7 is expressed by multiple vascular cell types in atherosclerosis, and ADAMTS7 promotes oxLDL uptake in smooth muscle cells, increasing smooth muscle foam cell formation and peripheral atherosclerosis in mice.

Profiles of resting state functional connectivity in temporal lobe epilepsy associated with post-laser interstitial thermal therapy seizure outcomes and semiologies.

Introduction: It is now understood that in focal epilepsy, impacted neural regions are not limited to the epileptogenic zone. As such, further investigation into the underlying functional connectivity (FC) patterns in those enduring Temporal Lobe Epilepsy (TLE) with Mesial Temporal Sclerosis (MTS) is imperative to understanding the intricacies of the disease. Methods: The rsfMRIs of 17 healthy participants, 10 left-sided TLE-MTS patients with a pre-operative history of focal impaired awareness seizures (FIA), and 13 left-sided TLE-MTS patients with a pre-operative history of focal aware seizures (FA) were compared to determine the existence of distinct FC patterns with respect to seizure types. Similarly, the rsfMRIs of the above-mentioned healthy participants, 16 left-sided TLE-MTS individuals who were seizure-free (SF) 12 months postoperatively, and 16 left-sided TLE-MTS persons without seizure freedom (nSF) were interrogated. The ROI-to-ROI connectivity analysis included a total of 175 regions of interest (ROIs) and accounted for both age and duration of epileptic activity. Significant correlations were determined via two-sample t-tests and Bonferroni correction (α = 0.05). Results: Comparisons of FA and FIA groups depicted significant correlations between the contralateral anterior cingulate gyrus, subgenual region, and the contralateral cerebellum, lobule III (p-value = 2.26e-4, mean z-score = -0.05 ± 0.28, T = -4.23). Comparisons of SF with nSF depicted two significantly paired-ROIs; the contralateral amygdala and the contralateral precuneus (p-value = 2.9e-5, mean z-score = -0.12 ± 0.19, T = 4.98), as well as the contralateral locus coeruleus and the ipsilateral intralaminar nucleus (p-value= 1.37e-4, mean z-score = 0.06 ± 0.17, T = -4.41). Significance: FC analysis proves to be a lucrative modality for exploring unique signatures with respect to seizure types and postoperative outcomes. By furthering our understanding of the differences between epileptic phenotypes, we can achieve improvement in future treatment modalities not limited to targeting advancements.

Case report: Utilizing diffusion-weighted MRI on a patient with chronic low back pain treated with spinal cord stimulation.

Diffusion-weighted magnetic resonance imaging (dwMRI) has increasingly demonstrated greater utility in analyzing neuronal microstructure. In patients with chronic low back pain (cLBP), using dwMRI to observe neuronal microstructure can lead to non-invasive biomarkers which could provide clinicians with an objective quantitative prognostic tool. In this case report, we investigated dwMRI for the development of non-invasive biomarkers by conducting a region-based analysis of a 55-year-old male patient with failed back surgery syndrome (FBSS) treated with spinal cord stimulation (SCS). We hypothesized that dwMRI could safely generate quantitative data reflecting cerebral microstructural alterations driven by neuromodulation. Neuroimaging was performed at 6- and 12- months post-SCS implantation. The quantitative maps generated included diffusion tensor imaging (DTI) parameters; fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) computed from whole brain tractography. To examine specific areas of the brain, 44 regions of interest (ROIs), collectively representing the pain NeuroMatrix, were extracted and registered to the patient's diffusion space. Average diffusion indices were calculated from the ROIs at both 6- and 12- months. Regions with >10% relative change in at least 3 of the 4 maps were reported. Using this selection criterion, 8 ROIs demonstrated over 10% relative changes. These ROIs were mainly located in the insular gyri. In addition to the quantitative data, a series of questionnaires were administered during the 6- and 12-month visits to assess pain intensity, functional disability, and quality of life. Overall improvements were observed in these components, with the Pain Catastrophizing Scale (PCS) displaying the greatest change. Lastly, we demonstrated the safety of dwMRI for a patient with SCS. In summary, the results from the case report prompt further investigation in applying dwMRI in a larger cohort to better correlate the influence of SCS with brain microstructural alterations, supporting the utility of dwMRI to generate non-invasive biomarkers for prognostication.

Automated subfield volumetric analysis of amygdala, hippocampus, and thalamic nuclei in mesial temporal lobe epilepsy.

Purpose: Identifying relationships between clinical features and quantitative characteristics of the amygdala-hippocampal and thalamic subregions in mesial temporal lobe epilepsy (mTLE) may offer insights into pathophysiology and the basis for imaging prognostic markers of treatment outcome. Our aim was to ascertain different patterns of atrophy or hypertrophy in mesial temporal sclerosis (MTS) patients and their associations with post-surgical seizure outcomes. To assess this aim, this study is designed in 2 folds: (1) hemispheric changes within MTS group and (2) association with postsurgical seizure outcomes. Methods and materials: 27 mTLE subjects with mesial temporal sclerosis (MTS) were scanned for conventional 3D T1w MPRAGE images and T2w scans. With respect to 12 months post-surgical seizure outcomes, 15 subjects reported being seizure free (SF) and 12 reported continued seizures. Quantitative automated segmentation and cortical parcellation were performed using Freesurfer. Automatic labeling and volume estimation of hippocampal subfields, amygdala, and thalamic subnuclei were also performed. The volume ratio (VR) for each label was computed and compared between (1) between contralateral and ipsilateral MTS using Wilcoxon rank-sum test and (2) SF and not seizure free (NSF) groups using linear regression analysis. False Discovery rate (FDR) with significant level of 0.05 were used in both analyses to correct for multiple comparisons. Results: Amygdala: The medial nucleus of the amygdala was the most significantly reduced in patients with continued seizures when compared to patients who remained seizure free. Hippocampus: Comparison of ipsilateral and contralateral volumes with seizure outcomes showed volume loss was most evident in the mesial hippocampal regions such as CA4 and hippocampal fissure. Volume loss was also most explicit in the presubiculum body in patients with continued seizures at the time of their follow-up. Ipsilateral MTS compared to contralateral MTS analysis showed the heads of the ipsilateral subiculum, presubiculum, parasubiculum, dentate gyrus, CA4, and CA3 were more significantly affected than their respective bodies. Volume loss was most noted in mesial hippocampal regions. Thalamus: VPL and PuL were the most significantly reduced thalamic nuclei in NSF patients. In all statistically significant areas, volume reduction was observed in the NSF group. No significant volume reductions were noted in the thalamus and amygdala when comparing ipsilateral to contralateral sides in mTLE subjects. Conclusions: Varying degrees of volume loss were demonstrated in the hippocampus, thalamus, and amygdala subregions of MTS, especially between patients who remained seizure-free and those who did not. The results obtained can be used to further understand mTLE pathophysiology. Clinical relevance/application: In the future, we hope these results can be used to deepen the understanding of mTLE pathophysiology, leading to improved patient outcomes and treatments.

The role of the insula in chronic pain following spinal cord injury: A resting-state fMRI study.

BACKGROUND AND PURPOSE: Spinal cord injury (SCI) results in the loss of motor and sensory function from disconnections between efferent and afferent pathways. Most SCI patients are affected with chronic neuropathic pain, but there is a paucity of data concerning neuroplastic changes following SCI. Chronic pain disrupts default networks and is associated with abnormal insular connectivity. The posterior insula (PI) is associated with the degree of pain and intensity of pain. The anterior insula (AI) is related to signal changes. Comprehension of SCI pain mechanisms is essential to elucidate effective treatment options. METHODS: This study examines the insular gyri functional connectivity (FC) of seven (five male, two female) SCI participants with moderate-severe chronic pain compared to 10 (five male, five female) healthy controls (HC). All subjects had 3-Tesla MRI performed and resting-state functional MRI (fMRI) was acquired. FC metrics were obtained from the comparisons of resting-state fMRI among our various groups. A seed-to-voxel analysis was pursued, encompassing six gyri of the insula. For multiple comparisons, a correction was applied with a significance level of p < .05. RESULTS: There were significant differences in FC of the insula between SCI participants with chronic pain compared with HC. In the SCI participants, there was hyperconnectivity of the AI and PI to the frontal pole. In addition, there was increased FC noted between the PI and the anterior cingulate cortex. Hyperconnectivity was also observed between the AI and the occipital cortex. CONCLUSIONS: These findings illustrate that there is a complex hyperconnectivity and modulation of pain pathways after traumatic SCI.

Resting-State fMRI Can Detect Alterations in Seizure Onset and Spread Regions in Patients with Non-Lesional Epilepsy: A Pilot Study.

Introduction: Epilepsy is defined as non-lesional (NLE) when a lesion cannot be localized via standard neuroimaging. NLE is known to have a poor response to surgery. Stereotactic electroencephalography (sEEG) can detect functional connectivity (FC) between zones of seizure onset (OZ) and early (ESZ) and late (LSZ) spread. We examined whether resting-state fMRI (rsfMRI) can detect FC alterations in NLE to see whether noninvasive imaging techniques can localize areas of seizure propagation to potentially target for intervention. Methods: This is a retrospective study of 8 patients with refractory NLE who underwent sEEG electrode implantation and 10 controls. The OZ, ESZ, and LSZ were identified by generating regions around sEEG contacts that recorded seizure activity. Amplitude synchronization analysis was used to detect the correlation of the OZ to the ESZ. This was also done using the OZ and ESZ of each NLE patient for each control. Patients with NLE were compared to controls individually using Wilcoxon tests and as a group using Mann-Whitney tests. Amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF), regional homogeneity (ReHo), degree of centrality (DoC), and voxel-mirrored homotopic connectivity (VMHC) were calculated as the difference between NLE and controls and compared between the OZ and ESZ and to zero. A general linear model was used with age as a covariate with Bonferroni correction for multiple comparisons. Results: Five out of 8 patients with NLE showed decreased correlations from the OZ to the ESZ. Group analysis showed patients with NLE had lower connectivity with the ESZ. Patients with NLE showed higher fALFF and ReHo in the OZ but not the ESZ, and higher DoC in the OZ and ESZ. Our results indicate that patients with NLE show high levels of activity but dysfunctional connections in seizure-related areas. Discussion: rsfMRI analysis showed decreased connectivity directly between seizure-related areas, while FC metric analysis revealed increases in local and global connectivity in seizure-related areas. FC analysis of rsfMRI can detect functional disruption that may expose the pathophysiology underlying NLE.

Automatic Segmentation of Parkinson Disease Therapeutic Targets Using Nonlinear Registration and Clinical MR Imaging: Comparison of Methodology, Presence of Disease, and Quality Control.

INTRODUCTION: Accurate and precise delineation of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) is critical for the clinical treatment and research of Parkinson's disease (PD). Automated segmentation is a developing technology which addresses limitations of visualizing deep nuclei on MR imaging and standardizing their definition in research applications. We sought to compare manual segmentation with three workflows for template-to-patient nonlinear registration providing atlas-based automatic segmentation of deep nuclei. METHODS: Bilateral GPi, STN, and red nucleus (RN) were segmented for 20 PD and 20 healthy control (HC) subjects using 3T MRIs acquired for clinical purposes. The automated workflows used were an option available in clinical practice and two common research protocols. Quality control (QC) was performed on registered templates via visual inspection of readily discernible brain structures. Manual segmentation using T1, proton density, and T2 sequences was used as "ground truth" data for comparison. Dice similarity coefficient (DSC) was used to assess agreement between segmented nuclei. Further analysis was done to compare the influences of disease state and QC classifications on DSC. RESULTS: Automated segmentation workflows (CIT-S, CRV-AB, and DIST-S) had the highest DSC for the RN and lowest for the STN. Manual segmentations outperformed automated segmentation for all workflows and nuclei; however, for 3/9 workflows (CIT-S STN, CRV-AB STN, and CRV-AB GPi) the differences were not statically significant. HC and PD only showed significant differences in 1/9 comparisons (DIST-S GPi). QC classification only demonstrated significantly higher DSC in 2/9 comparisons (CRV-AB RN and GPi). CONCLUSION: Manual segmentations generally performed better than automated segmentations. Disease state does not appear to have a significant effect on the quality of automated segmentations via nonlinear template-to-patient registration. Notably, visual inspection of template registration is a poor indicator of the accuracy of deep nuclei segmentation. As automatic segmentation methods continue to evolve, efficient and reliable QC methods will be necessary to support safe and effective integration into clinical workflows.

Accuracy and efficiency using frameless transient fiducial registration in stereoelectroencephalography and deep brain stimulation.

OBJECTIVE: Stereotactic surgical methods continue to advance technologically. Frameless transient fiducial registration (FTFR) systems have been developed and avoid the need to move or position a patient in a frame after already receiving registration imaging. One such system, Neurolocate, has recently become available as a robotic attachment for the Neuromate stereotactic robot. This study is the largest in the literature to evaluate the accuracy of frameless registration using Neurolocate versus frame-based registration (FBR) methods in both deep brain stimulation (DBS) and stereoelectroencephalography (SEEG). Additionally, the authors sought to reevaluate factors affecting accuracy in both procedures. METHODS: This study was a retrospective chart and imaging review of 88 consecutive procedures (involving 621 electrodes) implanting either DBS or SEEG at the authors' institution over a 5-year period from March 2015 to March 2020. Registration duration, radial target entry point, and Euclidean target implantation accuracies, as well as factors affecting accuracy, were recorded for each patient. RESULTS: SEEG procedures included 38 patients and 525 implanted electrodes (294 using FBR and 231 using FTFR). DBS procedures included 50 patients and 96 implanted electrodes (65 using FBR and 31 using FTFR). Overall, FTFR registration was significantly more accurate (median 0.1 mm, IQR 0-0.4 mm) compared with FBR (median 1.3 mm, IQR 0.9-1.5 mm; p = 0.04). Likewise, FTFR had a significantly shorter duration of registration (median 84 minutes, IQR 77.3-95.3 minutes) when compared with FBR (median 110.5 minutes, IQR 107.3-138 minutes; p = 0.02). No significant differences were found when examining the radial entry point and Euclidean target implantation errors of each method. CONCLUSIONS: FTFR with the Neurolocate system represents a technique that may decrease operative time while maintaining the high accuracy previously demonstrated by other stereotactic methods, despite an initial surgeon learning curve. It should be investigated in future studies to continue to improve stereotactic accuracies in neurosurgery.

Amplitude synchronization of spontaneous activity of medial and lateral temporal gyri reveals altered thalamic connectivity in patients with temporal lobe epilepsy.

In this study, we examined whether amplitude synchronization of medial (MTL) and lateral (LTL) temporal lobes can detect unique alterations in patients with MTL epilepsy (mTLE) with mesial temporal sclerosis (MTS). This was a retrospective study of preoperative resting-state fMRI (rsfMRI) data from 31 patients with mTLE with MTS (age 23-69) and 16 controls (age 21-35). fMRI data were preprocessed based on a multistep preprocessing pipeline and registered to a standard space. Using each subject's T1-weighted scan, the MTL and LTL were automatically segmented, manually revised and then fit to a standard space using a symmetric normalization registration algorithm. Dual regression analysis was applied on preprocessed rsfMRI data to detect amplitude synchronization of medial and lateral temporal segments with the rest of the brain. We calculated the overlapped volume ratio of synchronized voxels within specific target regions including the thalamus (total and bilateral). A general linear model was used with Bonferroni correction for covariates of epilepsy duration and age of patient at scan to statistically compare synchronization in patients with mTLE with MTS and controls, as well as with respect to whether patients remained seizure-free (SF) or not (NSF) after receiving epilepsy surgery. We found increased ipsilateral positive connectivity between the LTLs and the thalamus and contralateral negative connectivity between the MTLs and the thalamus in patients with mTLE with MTS compared to controls. We also found increased asymmetry of functional connectivity between temporal lobe subregions and the thalamus in patients with mTLE with MTS, with increased positive connectivity between the LTL and the lesional-side thalamus as well as increased negative connectivity between the MTL and the nonlesional-side thalamus. This asymmetry was also seen in NSF patients but was not seen in SF patients and controls. Amplitude synchronization was an effective method to detect functional connectivity alterations in patients with mTLE with MTS. Patients with mTLE with MTS overall showed increased temporal-thalamic connectivity. There was increased functional involvement of the thalamus in MTS, underscoring its role in seizure spread. Increased functional thalamic asymmetry patterns in NSF patients may have a potential role in prognosticating patient response to surgery. Elucidating regions with altered functional connectivity to temporal regions can improve understanding of the involvement of different regions in the disease to potentially target for intervention or use for prognosis for surgery. Future studies are needed to examine the effectiveness of using patient-specific abnormalities in patterns to predict surgical outcome.

Case report: The promising application of dynamic functional connectivity analysis on an individual with failed back surgery syndrome.

Failed back surgery syndrome (FBSS), a chronic neuropathic pain condition, is a common indication for spinal cord stimulation (SCS). However, the mechanisms of SCS, especially its effects on supraspinal/brain functional connectivity, are still not fully understood. Resting state functional magnetic resonance imaging (rsfMRI) studies have shown characteristics in patients with chronic low back pain (cLBP). In this case study, we performed rsfMRI scanning (3.0 T) on an FBSS patient, who presented with chronic low back and leg pain following her previous lumbar microdiscectomy and had undergone permanent SCS. Appropriate MRI safety measures were undertaken to scan this subject. Seed-based functional connectivity (FC) was performed on the rsfMRI data acquired from the FBSS subject, and then compared to a group of 17 healthy controls. Seeds were identified by an atlas of resting state networks (RSNs), which is composed of 32 regions grouped into 8 networks. Sliding-window method and k-means clustering were used in dynamic FC analysis, which resulted in 4 brain states for each group. Our results demonstrated the safety and feasibility of 3T MRI scanning in a patient with implanted SCS system. Compared to the brain states of healthy controls, the FBSS subject presented very different FC patterns in less frequent brain states. The mean dwell time of brain states showed distinct distributions: the FBSS subject seemed to prefer a single state over the others. Although future studies with large sample sizes are needed to make statistical conclusions, our findings demonstrated the promising application of dynamic FC to provide more granularity with FC changes associated with different brain states in chronic pain.

Digital Subtraction Angiography May Reduce the Rate of Radiographic Hemorrhage in Stereoelectroencephalography.

OBJECTIVE: To study the effect of preoperative digital subtractive angiography (DSA) for planning stereoelectroencephalography (sEEG) electrode trajectories on the rate of postoperative radiographic hemorrhage. METHODS: A retrospective, single-center observational study was conducted examining every sEEG implantation consisting of 72 implantations of 1028 total electrodes with each patient having received a preoperative planning DSA. Postimplant imaging was analyzed for the presence of hemorrhage. Postoperative computed tomography were then merged and coregistered with preoperative DSA to determine if a collision or near-miss (within 1 mm) occurred between the perihemorrhage electrodes and a vessel. Statistical analysis was then conducted. RESULTS: Six patients (8.3%) had hemorrhage seen on computed tomography with a bleeding rate of 0.6% per electrode. Five patients were asymptomatic (6.94%) and one symptomatic (1.39%). One patient suffered permanent neurologic deficits, and there have been zero deaths. In the hemorrhage group, there were 3 subdural, 2 subarachnoid, and 2 intraparenchymal. All subdural and subarachnoid hemorrhages had electrodes that were found to collide or near-miss a vessel when compared with preoperative DSA. Half of the intraparenchymal hemorrhages had no obvious vessel in proximity to the electrodes. Our data show that preoperative DSA is a viable screening test and portends a 94.7% sensitivity and 53.6% specificity for predicting post operative radiographic hemorrhage. CONCLUSIONS: Analysis of our sEEG series reveals a substantially lower rate of postimplant hemorrhage when compared with the recent cohort studies. Our data indicate that preoperative DSA may be efficacious in reducing the incidence of sEEG postimplant hemorrhages.

Use of Functional MRI in Deep Brain Stimulation in Parkinson's Diseases: A Systematic Review.

Deep brain stimulation (DBS) has been used to modulate aberrant circuits associated with Parkinson's disease (PD) for decades and has shown robust therapeutic benefits. However, the mechanism of action of DBS remains incompletely understood. With technological advances, there is an emerging use of functional magnetic resonance imaging (fMRI) after DBS implantation to explore the effects of stimulation on brain networks in PD. This systematic review was designed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to summarize peer-reviewed articles published within the past 10 years in which fMRI was employed on patients with PD-DBS. Search in PubMed database provided 353 references, and screenings resulted in a total of 19 studies for qualitative synthesis regarding study designs (fMRI scan timepoints and paradigm), methodology, and PD subtypes. This review concluded that fMRI may be used in patients with PD-DBS after proper safety test; resting-state and block-based fMRI designs have been employed to explore the effects of DBS on brain networks and the mechanism of action of the DBS, respectively. With further validation of safety use of fMRI and advances in imaging techniques, fMRI may play an increasingly important role in better understanding of the mechanism of stimulation as well as in improving clinical care to provide subject-specific neuromodulation treatments.

Minimally Invasive Sacroiliac Fusion-a Review.

PURPOSE OF REVIEW: Sacroiliac dysfunction is an important cause of low back pain with significant impact on quality of life and daily activities. Minimally invasive sacroiliac joint fusion (MIS SI fusion) is an effective treatment for patients who failed non-surgical strategies. The purpose of this article is to review the clinical outcomes and complications of this surgical technique. RECENT FINDINGS: For patients with SI joint dysfunction, MIS SI fusion reduced pain and disability as measured by Visual Analog Scale and Oswestry Index and improved quality of life as measured by Short-Form 36 and EuroQol-5D questionnaires. Satisfaction rates were higher in the SI fusion group when compared to the conservative management. In recent clinical trials, adverse events occurred with a similar rate in the first 6 months for patients assigned in the conservative management versus patients assigned to MIS SI fusion. MIS SI fusion is an effective and safe procedure for patients with sacroiliac dysfunction who failed non-surgical strategies. This procedure provides rapid as well as sustained pain relief, improvement in back function, high patient satisfaction, with low rate of complications.

The Impact of Intraoperative Image-Guidance Modalities and Neurophysiologic Monitoring in the Safety of Sacroiliac Fusions.

STUDY DESIGN: Retrospective observational cohort. OBJECTIVE: A review of efficiency and safety of fluoroscopy and stereotactic navigation system for minimally invasive (MIS) Sacroiliac (SI) fusion through a lateral technique. METHODS: Retrospective analysis of an observational cohort of 96 patients greater than 18 years old, that underwent MIS SI fusion guided by fluoroscopy or navigation between January 2013 and April 2020 with a minimum of 3 months follow-up. Intraoperative neuromonitoring (IONM) with a variable combination of electromyography (EMG), somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) was also utilized. RESULTS: The overall complication rate in the study was 9.4%, and there was no difference between the fluoroscopy (10.1%), and navigation groups (8%). Neurological complication rate was 2.1%, without a significant difference between both intraoperative guidance modality groups (p = 0.227). There was a significant difference between the modalities of IONM used and the occurrence of neurological injury (p = 0.01).The 2 patients who had a neurological complication postoperatively were monitored only with EMG and SSEP, but none of the patients (n = 76) in which MEPs were utilized had neurologic complication. The mean pain improvement 3 months after surgery was greater in the navigation group (2.44 ± 2.72), but was not statistically different than the improvement in the fluoroscopy group (1.90 ± 2.07) (p = 0.301). CONCLUSIONS: No difference in the safety of the procedure was found between the fluoroscopy and the stereotactic navigation techniques. The contribution of the IONM to the safety of SI fusions could not be determined, but the data indicates that MEPs provide the highest level of sensitivity.

Use of probabilistic tractography to provide reliable distinction of the motor and sensory thalamus for prospective targeting during asleep deep brain stimulation.

OBJECTIVE: Accurate electrode placement is key to effective deep brain stimulation (DBS). The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for the treatment of essential tremor (ET). Retrospective tractography-based analysis of electrode placement has associated successful outcomes with modulation of motor input to VIM, but no study has yet evaluated the feasibility and efficacy of prospective presurgical tractography-based targeting alone. Therefore, the authors sought to demonstrate the safety and efficacy of probabilistic tractography-based VIM targeting in ET patients and to perform a systematic comparison of probabilistic and deterministic tractography. METHODS: Fourteen patients with ET underwent preoperative diffusion imaging. Probabilistic tractography was applied for preoperative targeting, and deterministic tractography was performed as a comparison between methods. Tractography was performed using the motor and sensory areas as initiation seeds, the ipsilateral thalamus as an inclusion mask, and the contralateral dentate nucleus as a termination mask. Tract-density maps consisted of voxels with 10% or less of the maximum intensity and were superimposed onto anatomical images for presurgical planning. Target planning was based on probabilistic tract-density images and indirect target coordinates. Patients underwent robotic image-guided, image-verified implantation of directional DBS systems. Postoperative tremor scores with and without DBS were recorded. The center of gravity and Dice similarity coefficients were calculated and compared between tracking methods. RESULTS: Prospective probabilistic targeting of VIM was successful in all 14 patients. All patients experienced significant tremor reduction. Formal postoperative tremor scores were available for 9 patients, who demonstrated a mean 68.0% tremor reduction. Large differences between tracking methods were observed across patients. Probabilistic tractography-identified VIM fibers were more anterior, lateral, and superior than deterministic tractography-identified fibers, whereas probabilistic tractography-identified ventralis caudalis fibers were more posterior, lateral, and superior than deterministic tractography-identified fibers. Deterministic methods were unable to clearly distinguish between motor and sensory fibers in the majority of patients, but probabilistic methods produced distinct separation. CONCLUSIONS: Probabilistic tractography-based VIM targeting is safe and effective for the treatment of ET. Probabilistic tractography is more precise than deterministic tractography for the delineation of VIM and the ventralis caudalis nucleus of the thalamus. Deterministic algorithms tended to underestimate separation between motor and sensory fibers, which may have been due to its limitations with crossing fibers. Larger studies across multiple centers are necessary to further validate this method.

Costs Associated with Laser Interstitial Thermal Therapy Are Lower Than Anterior Temporal Lobectomy for Treatment of Temporal Lobe Epilepsy.

BACKGROUND: Laser interstitial thermal therapy (LITT) is a minimally invasive alternative to anterior temporal lobectomy (ATL) for treatment of temporal lobe epilepsy. It has gained popularity as familiarity with technique increases and outcomes are better characterized. There has been no direct cost comparison between the 2 techniques in literature to date. The current study directly compares hospital costs associated with LITT with those of ATL patients and analyzes the factors potentially responsible for those costs. METHODS: Patients who underwent ATL (27) and LITT (15) were retrospectively reviewed for total hospital costs along with demographic, surgical, and postoperative factors potentially affecting cost. T-tests were used to compare costs and independent linear regressions, and hierarchical regressions were used to examine predictors of cost for each procedure. RESULTS: Mean hospital costs of admission for single-trajectory LITT ($104,929.88) were significantly less than for ATL ($134,980.04) (P = 0.001). In addition, length of stay, anesthesia costs, operative room costs, and postoperative hospitalization costs were all significantly lower in LITT. CONCLUSIONS: Given the minimally invasive nature of LITT, it is associated with shorter length of stay and lower hospital costs than ATL in the first head-to-head comparison of procedural costs in literature to date. Long-term efficacy as it relates to these costs associated with LITT and ATL should be further investigated to better characterize the utility of LITT in temporal lobe epilepsy patients.

Adipocyte-specific tribbles pseudokinase 1 regulates plasma adiponectin and plasma lipids in mice.

OBJECTIVE: Multiple genome-wide association studies (GWAS) have identified SNPs in the 8q24 locus near TRIB1 that are significantly associated with plasma lipids and other markers of cardiometabolic health, and prior studies have revealed the roles of hepatic and myeloid Trib1 in plasma lipid regulation and atherosclerosis. The same 8q24 SNPs are additionally associated with plasma adiponectin levels in humans, implicating TRIB1 in adipocyte biology. Here, we hypothesize that TRIB1 in adipose tissue regulates plasma adiponectin, lipids, and metabolic health. METHODS: We investigate the metabolic phenotype of adipocyte-specific Trib1 knockout mice (Trib1_ASKO) fed on chow and high-fat diet (HFD). Through secretomics of adipose tissue explants and RNA-seq of adipocytes and livers from these mice, we further investigate the mechanism of TRIB1 in adipose tissue. RESULTS: Trib1_ASKO mice have an improved metabolic phenotype with increased plasma adiponectin levels, improved glucose tolerance, and decreased plasma lipids. Trib1_ASKO adipocytes have increased adiponectin production and secretion independent of the known TRIB1 function of regulating proteasomal degradation. RNA-seq analysis of adipocytes and livers from Trib1_ASKO mice indicates that alterations in adipocyte function underlie the observed plasma lipid changes. Adipose tissue explant secretomics further reveals that Trib1_ASKO adipose tissue has decreased ANGPTL4 production, and we demonstrate an accompanying increase in the lipoprotein lipase (LPL) activity that likely underlies the triglyceride phenotype. CONCLUSIONS: This study shows that adipocyte Trib1 regulates multiple aspects of metabolic health, confirming previously observed genetic associations in humans and shedding light on the further mechanisms by which TRIB1 regulates plasma lipids and metabolic health.