Tracking tumor evolution during the first-line treatment in brain glioma via serial profiling of cell-free tumor DNA from tumor in situ fluid.

Objective: Tumor in situ fluid (TISF) refers to the fluid within surgical cavities of glioma. Several studies preliminarily proved the value of cell-free tumor DNA (cf-tDNA) from TISF in the dynamic characterization of the glioma genome. Here, we assessed the potential utility of TISF cf-tDNA in broad aspects of tumor evolution under therapeutic pressure. Methods: This study was conducted under an Institutional Review Board-approved protocol at Henan Provincial People's Hospital (China). Cf-tDNA samples were sequenced with a designed 68-gene panel. A total of 205 cf-tDNA samples from 107 patients were studied. The clinical relevance of serial cf-tDNA profiling during the postoperative course was analyzed. Results: At least one tumor mutations were detected in 179/205 (87.3%) TISF cf-tDNA samples. Serial cf-tDNA was complementary to molecular residual disease and to initial tumors. Serial cf-tDNA revealed the selection of pre-existing mismatch repair-deficient cells by temozolomide as a resistant mechanism. Cf-tDNA parameters during treatment were predictive of recurrence, and serial cf-tDNA monitoring had diagnostic value for early recurrence. A total of 223 potentially actionable genomic alterations were assessed in cf-tDNA samples, wherein 78% were not found in any tumor tissue. Conclusions: In conclusion, serial TISF cf-tDNA profiling is valuable in tracking the tumor evolution of glioma during treatment and may be a feasible non-invasive option for monitoring glioma in future prospective studies and clinical practice.

Progressive Multifocal Encephalopathy Holmes Tremor Successfully Treated with Bilateral Deep Brain Stimulation.

Background: We report a patient with bilateral HT treated with DBS. Case report: A 58-year-old man diagnosed with HIV/AIDS and progressive multifocal leukoencephalopathy (PML) presented with 20 years of bilateral arm tremor refractory to therapy. DBS was implanted on the left ventral intermediate nucleus and posterior subthalamic area (VIM/PSA). One year later, a right VIM/PSA DBS was implanted. At twelve months, there were no significant side-effects. With his DBS turned off and on, the Fahn-Tolosa-Marin scale was rated 82 and 58, respectively. Discussion: To our knowledge, this is the first report of bilateral DBS VIM/PSA treating HT with no significant side effects. Highlights: We report a successful treatment using deep brain stimulation of bilateral Holmes tremor that was caused by progressive multifocal encephalopathy. The patient achieved 30% improvement in tremor control with a meaningful improvement in his activities of daily living.

Ogilvie's syndrome after paddle spinal cord stimulator implantation: An experience report.

Spinal cord stimulation (SCS) is an emerging technology to treat chronic pain from complex regional pain syndrome (CPRS) neuropathy and post-laminectomy syndrome. A rarely reported postoperative complication of SCS paddle implantation is abdominal pain that can result from thoracic radiculopathy. Ogilvie's syndrome (OS) is a disorder characterized by acute dilatation of the colon in the absence of an anatomic lesion that obstructs the flow of intestinal contents, which has seldom been observed after spine surgery. Here, we describe the case of a 70-year-old male who developed OS after SCS paddle implantation resulting in cecal perforation and multi-system organ failure with lethal outcome. We discuss the pathophysiology, present a method measuring the spinal canal to cord ratio (CCR) to prevent the risk of thoracic radiculopathy and OS after paddle SCS implantation, and propose suggestions for management and treatment of this condition.

Ipsilateral and axial tremor response to focused ultrasound thalamotomy for essential tremor: clinical outcomes and probabilistic mapping.

BACKGROUND: MR-guided focused ultrasound (MRgFUS) thalamotomy has been shown to be a safe and effective treatment for essential tremor (ET). OBJECTIVE: To investigate the effects of MRgFUS in patients with ET with an emphasis on ipsilateral-hand and axial tremor subscores. METHODS: Tremor scores and adverse effects of 100 patients treated between 2012 and 2018 were assessed at 1 week, 3, 12, and 24 months. A subgroup analysis of ipsilateral-hand tremor responders (defined as patients with ≥30% improvement at any time point) and non-responders was performed. Correlations and predictive factors for improvement were analysed. Weighted probabilistic maps of improvement were generated. RESULTS: Significant improvement in axial, contralateral-hand and total tremor scores was observed at all study visits from baseline (p<0.0001). There was no significant improvement in ipsilateral subscores. A subset of patients (n=20) exhibited group-level ipsilateral-hand improvement that remained significant through all follow-ups (p<0.001). Multivariate regression analysis revealed that higher baseline scores predict better improvement in ipsilateral-hand and axial tremor. Probabilistic maps demonstrated that the lesion hotspot for axial improvement was situated more medially than that for contralateral improvement. CONCLUSION: MRgFUS significantly improved axial, contralateral-hand and total tremor scores. In a subset of patients, a consistent group-level treatment effect was observed for ipsilateral-hand tremor. While ipsilateral improvement seemed to be less directly related to lesion location, a spatial relationship between lesion location and axial and contralateral improvement was observed that proved consistent with the somatotopic organisation of the ventral intermediate nucleus. TRIAL REGISTRATION NUMBERS: NCT01932463, NCT01827904, and NCT02252380.

Magnetically Guided Catheters, Micro- and Nanorobots for Spinal Cord Stimulation.

Spinal cord stimulation (SCS) is an established treatment for refractory pain syndromes and has recently been applied to improve locomotion. Several technical challenges are faced by surgeons during SCS lead implantation, particularly in the confined dorsal epidural spaces in patients with spinal degenerative disease, scarring and while targeting challenging structures such as the dorsal root ganglion. Magnetic navigation systems (MNS) represent a novel technology that uses externally placed magnets to precisely steer tethered and untethered devices. This innovation offers several benefits for SCS electrode placement, including enhanced navigation control during tip placement, and the ability to position and reposition the lead in an outpatient setting. Here, we describe the challenges of SCS implant surgery and how MNS can be used to overcome these hurdles. In addition to tethered electrode steering, we discuss the navigation of untethered micro- and nanorobots for wireless and remote neuromodulation. The use of these small-scale devices can potentially change the current standard of practice by omitting the need for electrode and pulse generator implantation or replacement. Open questions include whether small-scale robots can generate an electrical field sufficient to activate neuronal tissue, as well as testing precise navigation, placement, anchoring, and biodegradation of micro- and nanorobots in the in vivo environment.

Tumor DNA From Tumor In Situ Fluid Reveals Mutation Landscape of Minimal Residual Disease After Glioma Surgery and Risk of Early Recurrence.

The recurrence of glioma is a difficult problem in clinical treatment. The molecular markers of primary tumors after resection cannot fully represent the characteristics of recurrent tumors. Here, abundant tumor DNA was detected in tumor in situ fluid (TISF). We report that TISF-derived tumor DNA (TISF-DNA) can detect genomic changes in recurrent tumors and facilitate recurrence risk analysis, providing valuable information for diagnosis and prognosis. The tumor DNA in TISF is more representative and sensitive than that in cerebrospinal fluid. It reveals the mutational landscape of minimal residual disease after glioma surgery and the risk of early recurrence, contributing to the clinical management and clinical research of glioma patients.

Constrained-Spherical Deconvolution Tractography in the Evaluation of the Corticospinal Tract in Glioma Surgery.

Introduction: Tractography has demonstrated utility for surgical resection in the setting of primary brain tumors involving eloquent white matter (WM) pathways. Methods: Twelve patients with glioma in or near eloquent motor areas were analyzed. The motor status was recorded before and after surgery. Two different tractography approaches were used to generate the motor corticospinal tract (CST): Constrained spherical deconvolution probabilistic tractography (CSD-Prob) and single tensor deterministic tractography (Tens-DET). To define the degree of disruption of the CST after surgical resection of the tumor, we calculated the percentage of the CST affected by surgical resection, which was then correlated with the postoperative motor status. Moreover, the fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) of the CST generated by the CSD-Prob and the Tens-DET was measured and compared between the ipsilesional and contralesional side. Results: The CST was identified in all patients and its trajectory was displaced by the tumor. Only the CSD-Prob approach showed the CST with the characteristic fan-like projections from the precentral gyrus to the brainstem. Disruption of the CST was identified in 6/6 with postoperative motor deficit by CSD-Prob approach and in 5/6 in the Tens-DET. The degree of disruption was significantly associated with the motor deficit with the CSD-Prob approach (rho = -0.88, p = 0.021). However, with the Tens-DET approach the CST disruption did not show significant association with the motor function (rho = -0.27, p = 0.6). There was a significant decrease in FA (p = 0.006) and a significant increase in MD (p = 0.0004) and RD (p = 0.005) on the ipsilesional CST compared with the contralesional CST only with the CSD-Prob approach. Conclusion: CSD-Prob accurately represented the known anatomy of the CST and provided a meaningful estimate of microstructural changes of the CST affected by the tumor and its macrostructural damage after surgery. Newer surgical planning stations should include advanced models and algorithms of tractography in order to obtain more meaningful reconstructions of the WM pathways during glioma surgery.

Robotic Applications in Cranial Neurosurgery: Current and Future.

Robotics applied to cranial surgery is a fast-moving and fascinating field, which is transforming the practice of neurosurgery. With exponential increases in computing power, improvements in connectivity, artificial intelligence, and enhanced precision of accessing target structures, robots are likely to be incorporated into more areas of neurosurgery in the future-making procedures safer and more efficient. Overall, improved efficiency can offset upfront costs and potentially prove cost-effective. In this narrative review, we aim to translate a broad clinical experience into practical information for the incorporation of robotics into neurosurgical practice. We begin with procedures where robotics take the role of a stereotactic frame and guide instruments along a linear trajectory. Next, we discuss robotics in endoscopic surgery, where the robot functions similar to a surgical assistant by holding the endoscope and providing retraction, supplemental lighting, and correlation of the surgical field with navigation. Then, we look at early experience with endovascular robots, where robots carry out tasks of the primary surgeon while the surgeon directs these movements remotely. We briefly discuss a novel microsurgical robot that can perform many of the critical operative steps (with potential for fine motor augmentation) remotely. Finally, we highlight 2 innovative technologies that allow instruments to take nonlinear, predetermined paths to an intracranial destination and allow magnetic control of instruments for real-time adjustment of trajectories. We believe that robots will play an increasingly important role in the future of neurosurgery and aim to cover some of the aspects that this field holds for neurosurgical innovation.

Progress in robotics for combating infectious diseases.

The world was unprepared for the COVID-19 pandemic, and recovery is likely to be a long process. Robots have long been heralded to take on dangerous, dull, and dirty jobs, often in environments that are unsuitable for humans. Could robots be used to fight future pandemics? We review the fundamental requirements for robotics for infectious disease management and outline how robotic technologies can be used in different scenarios, including disease prevention and monitoring, clinical care, laboratory automation, logistics, and maintenance of socioeconomic activities. We also address some of the open challenges for developing advanced robots that are application oriented, reliable, safe, and rapidly deployable when needed. Last, we look at the ethical use of robots and call for globally sustained efforts in order for robots to be ready for future outbreaks.

Characterizing the Genomic Landscape of Brain Glioma With Circulating Tumor DNA From Tumor In Situ Fluid.

Tumor in situ fluid (TISF) refers to the fluid at the local surgical cavity. We evaluated the feasibility of TISF-derived circulating tumor DNA (ctDNA) characterizing the genomic landscape for glioma. This retrospective study included TISF and tumor samples from 10 patients with glioma, we extracted cell-free DNA (cfDNA) from the TISF and then performed deep sequencing on that. And we compared genomic alterations between TISF and tumor tissue. Results showed that the concentration of cfDNA fragments from the patients for TISF ranged from 7.2 to 1,397 ng/ml. At least one tumor-specific mutation was identified in all 10 patients (100%). Further analysis of TISF ctDNA revealed a broad spectrum of genetic mutations, which have been reported to have clinical relevance. The analysis of concordance between TISF and tumor tissue reflected the spatiotemporal heterogeneity of glioma. Collectively, TISF ctDNA was a powerfully potential source for characterizing the genomic landscape of glioma, which provided new possibilities for precision medicine in patients with glioma.

How to time the time - A preface to the special issue Circadian Rhythms in the Brain.

In this Preface to the Journal of Neurochemistry special issue "Circadian Rhythms in the Brain", we summarize recent insights into connections between circadian rhythms and societal concerns related to aging and food intake, with consequences for healthy or aberrant metabolic homeostasis. The articles in this special issue were written by leading authors who presented their research at the 2019 Congress of the European Biological Rhythm Society, and are thus reflective of a broad variety of state-of-the-art research on all levels of chronobiology, from circadian rhythm generators in various tissues (including astrocytes) and the molecular mechanisms they base on, such as GABAergic regulation or ubiquitination, to the systems and behavioral level effects of chrono-nutrition and aging. Cover Image for this issue: https://doi.org/10.1111/jnc.15058.

Laser thermal therapy for epilepsy surgery: current standing and future perspectives.

More than 130-year ago, Sir Victor Horsley delivered a landmark address to the British Medical Association, in which he described successful localization and resection of an epileptogenic focus resulting in seizure freedom for the patient. Several important steps in epilepsy surgery have been achieved since, including resection techniques such as anterior temporal lobectomy and selective amygdalohippocampectomy, both resulting in 70-80% seizure freedom and distinct differences in neuropsychological outcomes. The most recent addition to techniques for epilepsy surgery is minimally invasive thermal therapy. Significant advances in imaging technology and thermal ablation have opened a novel avenue for epilepsy treatment, permitting surgical intervention with seizure-freedom rates approaching the success of traditional methods but with reduced invasiveness, blood loss and duration of postoperative hospital stay. Here, we review recent advances on stereotactic ablation techniques focused on epilepsy surgery. Finally, we present emerging navigation techniques, which allow a higher degree of freedom. The described technologies render precise navigation of the ablation probe to avoid critical structures along the trajectory path and open novel pathways to further minimize invasiveness and improve safety and efficacy. Improve safety and efficacy.

3D path planning for flexible needle steering in neurosurgery.

BACKGROUND: We propose a 3D path planning method to steer flexible needles along curved paths in the context of deep brain stimulation (DBS) procedures. METHODS: Our approach is based on a rapidly exploring random tree strategy, and it takes into account constraints coming from anatomical obstacles and physical constraints dictated by flexible needle kinematics. The strategy is evaluated in simulation on a realistic 3D CAD model of the brain. RESULTS: The subthalamic nucleus (STN) and the fornix can be reached along several curved paths from various entry points. As compared with the usual straight line path, these curved paths avoid tissue damage to important neural structures while allowing for a much greater selection of entry points. CONCLUSIONS: This path planning method offers alternative curved paths to reach DBS targets with flexible needles. The method potentially leads to safer paths and additional entry points capable of reaching the desired stimulation targets.

Medical and surgical management of acute spinal injury during pregnancy: A case series in a third-world country.

BACKGROUND: There is scant literature describing the management of acute spinal injury in pregnant patients. Here, we report our experience with five cases of pregnant patients including three females who suffered acute traumatic spinal cord injuries (SCIs). METHODS: This retrospective study evaluated five pregnant women presenting with traumatic spinal injuries over a 16-month period. All were assessed using the International Standards for Neurological Classification of Spinal Cord Injury Patients and the American Spine Injury Association Impairment Scale (AIS). RESULTS: Three patients sustained SCIs: two cervical spine (C4 AIS-A and C5 AIS-B) and one thoracolumbar junction fracture dislocation (T11 AIS-A). Two patients required surgical stabilization during pregnancy, with one undergoing surgery after delivery. All three patients subsequently delivered healthy newborns. The remaining two patients without neurologic deficits at admission were treated conservatively; one had a healthy child, whereas the other patient aborted the baby due to the initial trauma. CONCLUSIONS: Our study demonstrates that the same surgical principals may be applied to pregnant women as to routine patients with SCIs. Further studies with greater patient data should be performed to better develop significant guidelines for the management of pregnant patients with spinal injuries.