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.

Mulberrin extends lifespan in Caenorhabditis elegans through detoxification function.

Mulberrin, a naturally occurring flavone found in mulberry and Romulus Mori, exhibits diverse biological functions. Here, we showed that mulberrin extended both the lifespan and healthspan in C. elegans. Moreover, mulberrin increased the worms' resistance to toxicants and activated the expression of detoxification genes. The longevity-promoting effect of mulberrin was attenuated in nuclear hormone receptor (NHR) homologous nhr-8 and daf-12 mutants, indicating that the lifespan extending effects of mulberrin in C. elegans may depend on nuclear hormone receptors NHR-8/DAF-12. Further analyses revealed the potential associations between the longevity effects of mulberrin and the insulin/insulin-like growth factor signaling (IIS) and adenosine 5'-monophosphate-activated protein kinase (AMPK) pathways. Together, our findings suggest that mulberrin may prolong lifespan and healthspan by activating detoxification functions mediated by nuclear receptors.

Thoracic canal morphology on preoperative magnetic resonance imaging in spinal cord stimulation patients.

INTRODUCTION: In high-frequency spinal cord stimulation anatomic placement targeting of the T9-10 disc space is based on "empiric" results that are best replicated with coverage broadly from T8 to T10. This study contains the largest cohort of patients evaluating low thoracic morphology and seeks to address the lack of MRI morphological analysis in literature. METHODS: This study was a retrospective review of a database of 101 consecutive patients undergoing permanent implant of thoracic SCS for chronic pain. Measurements were carried out on preoperative MRI imaging. Anteroposterior (AP) and lateral dimensions of the spinal cord as well as dural sac were measured. In addition, dorsal cerebrospinal fluid thickness and paddle depression distance were also measured. RESULTS: When comparing morphological dimensions by level, dorsal CSF thickness was smaller at T9-10 than T7-8 (p = 0.018). In addition, lateral dural and spinal cord diameters were larger at T10-11 than T9-10, contributing to larger dural surface area at T10-11 (p = 0.028). While trends of dorsal CSF thickness tend to decrease with lower thoracic levels, the ratio of surface area of spinal cord to dural sac appeared to remain relatively constant. CONCLUSIONS: Dorsal CSF thickness is smaller at T9-10 than T7-8 in chronic pain patients in this cohort. More ellipsoid, cord, and spinal canal diameter measurements were noted at lower levels of the thoracic spinal cord, particularly at T10-11. This may correlate with anatomical SCS placement. Future studies should evaluate efficacy of SCS therapy for pain based on these anatomical considerations.

[Preparation of vitexin albumin nanoparticles and its pharmacokinetic study].

This study aims to prepare vitexin albumin nanoparticles(VT-BSA-NPs) to alleviate the low bioavailability of vitexin(VT) in vivo due to its poor water solubility. VT micro powders were prepared by the antisolvent crystallization method, and the morphology, size, and physicochemical properties of VT micro powders were studied. The results showed that the VT micro powder had a particle size of(187.13±7.15) nm, an approximate spherical morphology, and a uniform size distribution. Compared with VT, the chemical structure of VT micro powders has not changed. VT-BSA-NPs were prepared from VT micro powders by desolvation-crosslinking curing method. The preparation process was screened by single factor test and orthogonal test, and the quality evaluation of the optimal prescription particle size, PDI, Zeta potential, EE, and morphology was performed. The results showed that the average particle size of VT-BSA-NPs was(124.33±0.47) nm; the PDI was 0.184±0.012; the Zeta potential was(-48.83±2.20) mV, and the encapsulation rate was 83.43%±0.39%, all of which met the formulation-related requirements. The morphological results showed that the VT-BSA-NPs were approximately spherical in appearance, regular in shape, and without adhesion on the surface. In vitro release results showed a significantly reduced release rate of VT-BSA-NPs compared with VT, indicating a good sustained release effect. LC-MS/MS was used to establish an analytical method for in vivo analysis of VT and study the plasma pharmacokinetics of VT-BSA-NPs in rats. The results showed that the specificity of the analytical method was good, and the extraction recovery was more than 90%. Compared with VT and VT micro powders, VT-BSA-NPs could significantly increase AUC, MRT, and t_(1/2), which was beneficial to improve the bioavailability of VT.

The Temporal Lobe Club: Newer Approaches to Treat Temporal Lobe Epilepsy.

This brief review summarizes presentations at the Temporal Lobe Club Special Interest Group session held in December 2022 at the American Epilepsy Society meeting. The session addressed newer methods to treat temporal epilepsy, including methods currently in clinical use and techniques under investigation. Brief summaries are provided for each of 4 lectures. Dr Chengyuan Wu discussed ablative techniques such as laser interstitial thermal ablation, radiofrequency ablation, focused ultrasound; Dr Joon Kang reviewed neuromodulation techniques including electrical stimulation and focused ultrasound; Dr Julia Makhalova discussed network effects of the aforementioned techniques; and Dr Derek Southwell reviewed inhibitory interneuron transplantation. These summaries are intended to provide a brief overview and references are provided for the reader to learn more about each topic.

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.

Demographics and PainDETECT as Predictors of 24-Month Outcomes for 10 kHz SCS in Nonsurgical Refractory Back Pain.

BACKGROUND: Nonsurgical refractory back pain (NSRBP) is broadly defined as chronic refractory back pain in patients who have not had previous spine surgery and, because they are deemed inappropriate candidates for surgery, are reliant on conventional medical management (CMM), which often provides poor long-term outcomes. High-frequency spinal cord stimulation (10kHz SCS) has demonstrated high rates of pain relief and improvements in functioning in patients with NSRBP. However, despite the use of temporary trial stimulation to select patients who will respond to therapy, some patients fail to achieve long-term therapy response with permanent implants. Prediction analysis founded on patients' baseline characteristics may enrich the appropriate selection of patients for permanent implantation. OBJECTIVES: To examine baseline patient characteristics to predict long-term pain and functional responses to treatment with 10 kHz SCS for NSRBP. STUDY DESIGN: A retrospective analysis of baseline patient characteristics as predictors of 24-month pain and functional outcomes from a previous multicenter randomized controlled trial of 10 kHz SCS in patients with NSRBP. PATIENTS: Patients diagnosed with chronic, neuropathic, axial, low back pain refractory to CMM who had had no previous spine surgery, were deemed unsuitable candidates for it according to a spine surgeon, were implanted with 10kHz SCS and continued with CMM for up to 24 months. METHODS: The baseline characteristics of and 24-month outcomes in the 125 implanted patients who participated in the NSRBP randomized controlled trial (RCT) were included in this analysis. The baseline characteristics included demographics, baseline pain on the visual analog scale (VAS), baseline function based on the Oswestry Disability Index (ODI), mental health according to the patient health questionnaire-9 (PHQ-9), neuropathic pain as measured by PainDETECT, and each patient's temporary trial response. Patient response at 24 months was defined as absolute change from the baseline on the VAS and ODI, and each patient was also classified as a pain responder (achieving at least a 50% decrease in VAS pain score from the baseline) and a function responder (at least a 10-point decrease in ODI or a 24-month score of no more than 20 points). Multivariate prediction models based on regression and classification and regression tree (CART) techniques were developed using the response variables discussed above as the dependent variables and the baseline characteristics as the independent variables. RESULTS: Different factors contributed to pain and functional outcomes. Patients presenting with neuropathic pain (PainDETECT >= 19) and female gender had higher odds of being pain responders to 10 kHz SCS therapy than did males and those without neuropathic pain. Both higher age and depression score (PHQ-9) independently reduced the odds that a patient would be an ODI responder. Years since diagnosis, the reason the patient was deemed unsuitable for spine surgery, and pain etiology were not predictive of pain or functional outcomes. LIMITATIONS: A retrospective sub-analysis of a single pragmatic randomized controlled trial. CONCLUSIONS: There may be an opportunity to increase pain relief and functional improvement if additional patient screening accompanies the temporary lead trial. The presence of neuropathic pain, female gender, age, and depression had some predictive value, but this analysis demonstrates the treatment efficacy of 10 kHz SCS across a wide range of patients with NSRBP.

Facile Electret-Based Self-Powered Soft Sensor for Noncontact Positioning and Information Translation.

Noncontact sensors have demonstrated significant potential in human-machine interactions (HMIs) in terms of hygiene and less wear and tear. The development of soft, stable, and simply structured noncontact sensors is highly desired for their practical applications in HMIs. This work reports on electret-based self-powered noncontact sensors that are soft, transparent, stable, and easy to manufacture. The sensors contain a three-layer structure with a thickness of 0.34 mm that is fabricated by simply stacking a polymeric electret layer, an electrode layer, and a substrate layer together. The fabricated sensors show high charge-retention capability, keeping over 98% of the initial surface potential even after 90 h, and can accurately and repeatedly sense external approaching objects with impressive durability. The intensity of the detected signal shows a strong dependence on the distance between the object and the sensor, capable of sensing a distance as small as 2 mm. Furthermore, the sensors can report stable signals in response to external objects over 3000 cycles. By virtue of the signal dependence on distance, an intelligent noncontact positioning system is developed that can precisely detect the location of an approaching object. Finally, by integrating with eyeglasses, the transparent sensor successfully captures the movements of blinks for information translation. This work may contribute to the development of stable and easily manufactured noncontact soft sensors for HMI applications, for instance, assisting with communication for locked-in syndrome patients.

Magnolol extends lifespan and improves age-related neurodegeneration in Caenorhabditis elegans via increase of stress resistance.

Magnolol is a naturally occurring polyphenolic compound in many edible plants, which has various biological effects including anti-aging and alleviating neurodegenerative diseases. However, the underlying mechanism on longevity is uncertain. In this study, we investigated the effect of magnolol on the lifespan of Caenorhabditis elegans and explored the mechanism. The results showed that magnolol treatment significantly extended the  lifespan of nematode and alleviated senescence-related decline in the nematode model. Meanwhile, magnolol enhanced stress resistance to heat shock, hydrogen peroxide (H2O2), mercuric potassium chloride (MeHgCl) and paraquat (PQ) in nematode. In addition, magnolol reduced reactive oxygen species and malondialdehyde (MDA) levels, and increased superoxide dismutase and catalase (CAT) activities in nematodes. Magnolol also up-regulated gene expression of sod-3, hsp16.2, ctl-3, daf-16, skn-1, hsf-1, sir2.1, etc., down-regulated gene expression of daf-2, and promoted intranuclear translocation of daf-16 in nematodes. The lifespan-extending effect of magnolol were reversed in insulin/IGF signaling (IIS) pathway-related mutant lines, including daf-2, age-1, daf-16, skn-1, hsf-1 and sir-2.1, suggesting that IIS signaling is involved in the modulation of longevity by magnolol. Furthermore, magnolol improved the age-related neurodegeneration in PD and AD C. elegans models. These results indicate that magnolol may enhance lifespan and health span through IIS and sir-2.1 pathways. Thus, the current findings implicate magnolol as a potential candidate to ameliorate the symptoms of aging.

MscI restriction enzyme cooperating recombinase-aided isothermal amplification for the ultrasensitive and rapid detection of low-abundance EGFR mutations on microfluidic chip.

The detection of low-abundance mutation genes of the epidermal growth factor receptor (EGFR) exon 21 (EGFR L858R) plays a crucial role in the diagnosis of non-small cell lung cancer (NSCLC), as it enables early cancer detection and facilitates the development of treatment strategies. A detection platform was developed by combining the MscI restriction enzyme with the recombinase-aided isothermal amplification (RAA) technique (MRE-RAA). During the RAA process, "TGG^CCA" site of the wild-type genes was cleaved by the MscI restriction enzyme, while only the low-abundance mutation genes underwent amplification. Notably, when the RAA product was combined with CRISPR-Cas system, the sensitivity of detecting the EGFR L858R mutation increased by up to 1000-fold for addition of the MscI restriction enzyme. This achievement marked the first instance of attaining an analytical sensitivity of 0.001%. Furthermore, a disk-shaped microfluidic chip was developed to automate pretreatment while concurrently analyzing four blood samples. The microfluidic features of the chip include DNA extraction, MRE-RAA, and CRISPR-based detection. The fluorescence signal is employed for detection in the microfluidic chip, which is visible to the naked eye upon exposure to blue light irradiation. Furthermore, this platform has the capability to facilitate early diagnosis for various types of cancer by enabling high-sensitivity detection of low-abundance mutation genes.

Simulated resections and RNS placement can optimize post-operative seizure outcomes when guided by fast ripple networks.

In medication-resistant epilepsy, the goal of epilepsy surgery is to make a patient seizure free with a resection/ablation that is as small as possible to minimize morbidity. The standard of care in planning the margins of epilepsy surgery involves electroclinical delineation of the seizure onset zone (SOZ) and incorporation of neuroimaging findings from MRI, PET, SPECT, and MEG modalities. Resecting cortical tissue generating high-frequency oscillations (HFOs) has been investigated as a more efficacious alternative to targeting the SOZ. In this study, we used a support vector machine (SVM), with four distinct fast ripple (FR: 350-600 Hz on oscillations, 200-600 Hz on spikes) metrics as factors. These metrics included the FR resection ratio (RR), a spatial FR network measure, and two temporal FR network measures. The SVM was trained by the value of these four factors with respect to the actual resection boundaries and actual seizure free labels of 18 patients with medically refractory focal epilepsy. Leave one out cross-validation of the trained SVM in this training set had an accuracy of 0.78. We next used a simulated iterative virtual resection targeting the FR sites that were highest rate and showed most temporal autonomy. The trained SVM utilized the four virtual FR metrics to predict virtual seizure freedom. In all but one of the nine patients seizure free after surgery, we found that the virtual resections sufficient for virtual seizure freedom were larger in volume (p<0.05). In nine patients who were not seizure free, a larger virtual resection made five virtually seizure free. We also examined 10 medically refractory focal epilepsy patients implanted with the responsive neurostimulator system (RNS) and virtually targeted the RNS stimulation contacts proximal to sites generating FR at highest rates to determine if the simulated value of the stimulated SOZ and stimulated FR metrics would trend toward those patients with a better seizure outcome. Our results suggest: 1) FR measures can accurately predict whether a resection, defined by the standard of care, will result in seizure freedom; 2) utilizing FR alone for planning an efficacious surgery can be associated with larger resections; 3) when FR metrics predict the standard of care resection will fail, amending the boundaries of the planned resection with certain FR generating sites may improve outcome; and 4) more work is required to determine if targeting RNS stimulation contact proximal to FR generating sites will improve seizure outcome.

Epilepsy Networks and Their Surgical Relevance.

Surgical epilepsy is a rapidly evolved field. As the understanding and concepts of epilepsy shift towards a network disorder, surgical outcomes may shed light on numerous components of these systems. This review documents the evolution of the understanding of epilepsy networks and examines the data generated by resective, ablative, neuromodulation, and invasive monitoring surgeries in epilepsy patients. As these network tools are better integrated into epilepsy practice, they may eventually inform surgical decisions and improve clinical outcomes.

Brain Lesion Synthesis via Progressive Adversarial Variational Auto-Encoder.

Laser interstitial thermal therapy (LITT) is a novel minimally invasive treatment that is used to ablate intracranial structures to treat mesial temporal lobe epilepsy (MTLE). Region of interest (ROI) segmentation before and after LITT would enable automated lesion quantification to objectively assess treatment efficacy. Deep learning techniques, such as convolutional neural networks (CNNs) are state-of-the-art solutions for ROI segmentation, but require large amounts of annotated data during the training. However, collecting large datasets from emerging treatments such as LITT is impractical. In this paper, we propose a progressive brain lesion synthesis framework (PAVAE) to expand both the quantity and diversity of the training dataset. Concretely, our framework consists of two sequential networks: a mask synthesis network and a mask-guided lesion synthesis network. To better employ extrinsic information to provide additional supervision during network training, we design a condition embedding block (CEB) and a mask embedding block (MEB) to encode inherent conditions of masks to the feature space. Finally, a segmentation network is trained using raw and synthetic lesion images to evaluate the effectiveness of the proposed framework. Experimental results show that our method can achieve realistic synthetic results and boost the performance of down-stream segmentation tasks above traditional data augmentation techniques.