Spinal Cord Stimulation Meets Them All: An Effective Treatment for Different Pain Conditions. Our Experience and Literature Review.

IntroductionSpinal Cord Stimulation (SCS) is an emerging minimally invasive technique which uses neuromodulation to manage different forms of intractable pain. SCS is a well-established option for the treatment of various pain conditions, and nowadays, indications are ever increasing.Materials and MethodsIn this study, we present our case series of 49 patients who underwent SCS at our Institution for the treatment of pain from different etiologies, and discuss our 10-year experience in SCS. For the purpose of this study, we also performed a systematic review of current indications and new perspectives in SCS.ResultsAmong our case series, patients were differentiated into two groups upon prior spinal surgery: patients who had undergone prior spinal surgery for back pain were defined as the "FBSS (failed back surgery syndrome) group," instead patient suffering from different types of pain but who had never undergone surgery were defined as the "naive group." As regards clinical response to SCS, 20 patients out of 36 (55.56%) were classified as responders in the FBSS group; in the "naïve" group, 10 patients out of 13 (76.92%) were classified as responders. Among the "not responders" group, several patients suffered from infections.Of the recent literature about SCS, 2124 records were screened and 37 studies were finally included in the qualitative synthesis for our systematic review.DiscussionIn case of FBSS, surgical revision is often associated with a high morbidity and corresponding low rates of success. Unfortunately, patients affected by chronic pain often become refractory to conservative treatments. Spinal Cord Stimulation (SCS) is nowadays considered as an effective therapy for several chronic and neuropathic pain conditions, such as failed back surgery syndrome. As regards the economic impact of SCS, implantation of an SCS system results in short-term costs increase, but the annual cumulative costs decrease during the following years after implantation, when compared to the costs of conventional management. Beyond the application for the treatment of FBSS, SCS has also been used for the treatment of other types of chronic non-oncological pain such as neuropathic pain and chronic back pain ineligible for surgical intervention. This evidence paved the way to establishing the potential role of SCS also for the treatment of oncological pain. However, the effectiveness and relative safety of SCS for cancer-related pain has not yet been adequately established.ConclusionsSpinal Cord Stimulation is a well-established treatment option in for FBSS. Beyond that, SCS has also been used for the treatment of "naive" patients, suffering from other types of chronic, both oncological and non-oncological, medical-refractory pain such as neuropathic pain and chronic back pain ineligible for surgical intervention.

Pedicle Screw Placement Aided by C-Arm Fluoroscopy: A "Nevermore without" Technology to Pursue Optimal Spine Fixation.

The surgical technique and the intraoperative technology that support spinal pedicle screw placement have consistently evolved over the past decades to decrease the misplacement rate of pedicle screws. We retrospectively evaluated our case series by analyzing the period 2016-2020. Patients undergoing pedicle screw fixation for cervical, thoracic, or lumbar spine degenerative diseases have been included. Surgery was carried out with the aid of intraoperative 3D C-arm fluoroscopy to assess and optimize screw placement and/or correct possible mispositioning. Each patient underwent a postoperative CT scan. Our aim was to evaluate the safety and accuracy of pedicle screw placement and estimate the variation in mispositioning rates. We carried out 329 surgical procedures, as follows: 70 cervical, 78 thoracic spine, and 181 lumbar spine surgeries. An excellent overall pedicle screw positioning was obtained, with slight differences between the cervical (98.6%), thoracic (100%), and lumbar (98.9%) tracts. Accordingly, only three patients required a revision surgery owing to mispositioning (0.91%). In particular, intraoperative C-arm fluoroscopy significatively improved the accuracy of thoracic screw positioning, as shown by postoperative CT scans. Our experience proves the crucial role of intraoperative C-arm fluoroscopy in pursuing optimal technical results and improving patient outcomes at follow-up.

Assessing the Training in Neurosurgery with the Implementation of VITOM-3D Exoscope: Learning Curve on Experimental Model in Neurosurgical Practice.

(1) Background: Innovation and continuous demand in the field of visual enhancing technologies and video streaming have led to the discovery of new systems capable of improving visualization and illumination of the surgical field. The exoscope was brought into neurosurgical routine, and nearly ten years later, modern 3D systems have been introduced and tested, giving encouraging results. (2) Methods: In order to evaluate the surgeon's confidence with the exoscope and their increasing ability in terms of time spent and quality of the final achievement since their first encounter with the technique, an experimental trial on 18 neurosurgeons from a single Institution was performed to evaluate the learning curve for the use of the VITOM-3D exoscope in neurosurgical practice on a model of brain and dura mater. (3) Results: A significant improvement in the quality of the performance, number of errors made, and reduction in the time was found after the third iteration of the task, by when almost all the participants felt more comfortable and confident. No significant differences between senior neurosurgeons and resident neurosurgeons were reported. (4) Conclusions: Our results show that three iterations are enough to gain confidence with the exoscope from its first use, regardless of previous experience and training with an operating microscope.

The Role of Aquaporins in Epileptogenesis-A Systematic Review.

Aquaporins (AQPs) are a family of membrane proteins involved in the transport of water and ions across cell membranes. AQPs have been shown to be implicated in various physiological and pathological processes in the brain, including water homeostasis, cell migration, and inflammation, among others. Epileptogenesis is a complex and multifactorial process that involves alterations in the structure and function of neuronal networks. Recent evidence suggests that AQPs may also play a role in the pathogenesis of epilepsy. In animal models of epilepsy, AQPs have been shown to be upregulated in regions of the brain that are involved in seizure generation, suggesting that they may contribute to the hyperexcitability of neuronal networks. Moreover, genetic studies have identified mutations in AQP genes associated with an increased risk of developing epilepsy. Our review aims to investigate the role of AQPs in epilepsy and seizure onset from a pathophysiological point of view, pointing out the potential molecular mechanism and their clinical implications.

The role of neuronal plasticity in cervical spondylotic myelopathy surgery: functional assessment and prognostic implication.

Cervical spondylotic myelopathy (CSM) is a degenerative disease representing the most common spinal cord disorder in the adult population. It is characterized by chronic compression leading to neurological dysfunction due to static and dynamic injury of the spinal cord in cervical spine. These insidious damage mechanisms can result in the reorganization of cortical and subcortical areas. The cerebral cortex can reorganize due to spinal cord injury and may play a role in preserving neurological function. To date, the gold standard treatment of cervical myelopathy is surgery, comprising anterior, posterior, and combined approaches. However, the complex physiologic recovery processes involving cortical and subcortical neural reorganization following surgery are still inadequately understood. It has been demonstrated that diffusion MRI and functional imaging and techniques, such as transcranial magnetic stimulation (TMS) or functional magnetic resonance imaging (fMRI), can provide new insights into the diagnosis and prognosis of CSM. This review aims to shed light on the state-of-the-art regarding the pattern of cortical and subcortical areas reorganization and recovery before and after surgery in CSM patients, underlighting the critical role of neuroplasticity.

Forecasting Molecular Features in IDH-Wildtype Gliomas: The State of the Art of Radiomics Applied to Neurosurgery.

BACKGROUND: The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, marks a step forward the future diagnostic approach to these neoplasms. Alongside this, radiomics has experienced rapid evolution over the last several years, allowing us to correlate tumor imaging heterogeneity with a wide range of tumor molecular and subcellular features. Radiomics is a translational field focused on decoding conventional imaging data to extrapolate the molecular and prognostic features of tumors such as gliomas. We herein analyze the state-of-the-art of radiomics applied to glioblastoma, with the goal to estimate its current clinical impact and potential perspectives in relation to well-rounded patient management, including the end-of-life stage. METHODS: A literature review was performed on the PubMed, MEDLINE and Scopus databases using the following search items: "radiomics and glioma", "radiomics and glioblastoma", "radiomics and glioma and IDH", "radiomics and glioma and TERT promoter", "radiomics and glioma and EGFR", "radiomics and glioma and chromosome". RESULTS: A total of 719 articles were screened. Further quantitative and qualitative analysis allowed us to finally include 11 papers. This analysis shows that radiomics is rapidly evolving towards a reliable tool. CONCLUSIONS: Further studies are necessary to adjust radiomics' potential to the newest molecular requirements pointed out by the 2021 WHO classification of CNS tumors. At a glance, its application in the clinical routine could be beneficial to achieve a timely diagnosis, especially for those patients not eligible for surgery and/or adjuvant therapies but still deserving palliative and supportive care.

Intraoperative Evaluation of Brain-Tumor Microvascularization through MicroV IOUS: A Protocol for Image Acquisition and Analysis of Radiomic Features.

Microvascular Doppler (MicroV) is a new-generation Doppler technique developed by Esaote (Esaote s.p.a., Genova, Italy), which is able to visualize small and low-flow vessels through a suppression of interfering signals. MicroV uses advanced filters that are able to differentiate tissue artifacts from low-speed blood flows; by exploiting the space-time coherence information, these filters can selectively suppress tissue components, preserving the signal coming from the microvascular flow. This technique is clinically applied to the study of the vascularization of parenchymatous lesions, often with better diagnostic accuracy than color/power Doppler techniques. The aim of this paper is to develop a reproducible protocol for the recording and collection of MicroV intraoperative ultrasound images by the use of a capable intraoperative ultrasound machine and post-processing aimed at evaluation of brain-tumor microvascularization through the analysis of radiomic features. The proposed protocol has been internally validated on eight patients and will be firstly applied to patients affected by WHO grade IV astrocytoma (glioblastoma-GBM) candidates for craniotomy and lesion removal. In a further stage, it will be generally applied to patients with primary or metastatic brain tumors. IOUS is performed before durotomy. Tumor microvascularization is evaluated using the MicroV Doppler technique and IOUS images are recorded, stored, and post-processed. IOUS images are remotely stored on the BraTIoUS database, which will promote international cooperation and multicentric analysis. Processed images and texture radiomic features are analyzed post-operatively using ImageJ, a free scientific image-analysis software based on the Sun-Java platform. Post-processing protocol is further described in-depth. The study of tumor microvascularization through advanced IOUS techniques such as MicroV could represent, in the future, a non-invasive and real-time method for intraoperative predictive evaluation of the tumor features. This evaluation could finally result in a deeper knowledge of brain-tumor behavior and in the on-going adaptation of the surgery with the improvement of surgical outcomes.

Updated Systematic Review on the Role of Brain Invasion in Intracranial Meningiomas: What, When, Why?

Several recent studies are providing increasing insights into reliable markers to improve the diagnostic and prognostic assessment of meningioma patients. The evidence of brain invasion (BI) signs and its associated variables has been focused on, and currently, scientific research is investing in the study of key aspects, different methods, and approaches to recognize and evaluate BI. This paradigm shift may have significant repercussions for the diagnostic, prognostic, and therapeutic approach to higher-grade meningioma, as long as the evidence of BI may influence patients' prognosis and inclusion in clinical trials and indirectly impact adjuvant therapy. We intended to review the current knowledge about the impact of BI in meningioma in the most updated literature and explore the most recent implications on both clinical practice and trials and future directions. According to the PRISMA guidelines, systematic research in the most updated platform was performed in order to provide a complete overview of characteristics, preoperative applications, and potential implications of BI in meningiomas. Nineteen articles were included in the present paper and analyzed according to specific research areas. The detection of brain invasion could represent a crucial factor in meningioma patients' management, and research is flourishing and promising.

The Long and Winding Road: An Overview of the Immunological Landscape of Intracranial Meningiomas.

The role of immunotherapy is gaining ever-increasing interest in the neuro-oncological field, and this is also expanding to the management of intracranial meningioma. Meningiomas are still the most common primary adult tumor of the CNS, and even though surgery and/or radiotherapy still represent cornerstones of their treatment, recent findings strongly support the potential role of specific immune infiltrate cells, their features and genomics, for the application of personalized treatments and prognostic implications. According to the PRISMA guidelines, systematic research in the most updated platform was performed in order to provide a descriptive and complete overview about the characteristics, role and potential implications of immunology in meningioma tumors. Seventy articles were included and analyzed in the present paper. The meningioma microenvironment reveals complex immune tumor-immune cells interactions that may definitely influence tumor progression, as well as offering unexpected opportunities for treatment.

Thoracic dumbbell spinal metastasis secondary to neuroendocrine tumor of unknown origin: Case report and literature review.

Background: Dumbbell tumors are typically benign schwannomas, neurofibromas, and meningiomas and only rarely there are malignant variants of these lesions or other malignant histotypes. Here, a 34-year-old male presented with a thoracic spinal dumbbell metastatic neuroendocrine carcinoma of unknown primary origin. Case Description: A 34-year-old male presented with 2 months of thoracic pain and progressive mid thoracic sensory loss. A post contrast thoracic MRI showed a dumbbell tumor localized between the T7 and T9 levels with extension laterally into the T7-T8 and T8-T9 foramina. The patient underwent a laminectomy for tumor resection following which his pain and gait improved. Histopathologically, the tumor demonstrated multiple rounded small cells with a Ki67 level around 30%, suggesting a malignant metastatic neuroendocrine tumor of unknown etiology. Conclusion: We successfully treated a 34-year-old male with a T7-T9 malignant spinal dumbbell neuroendocrine tumor of unknown etiology utilizing a decompressive laminectomy.

Spinal Tractography as a Potential Prognostic Tool in Spinal Cord Injury: A Systematic Review.

Magnetic resonance imaging is considered the most accurate examination to study the spinal cord. Nevertheless, the use of diffusion tensor imaging (DTI) can demonstrate additional key details about spinal cord lesions. We examined the literature to investigate and discuss the role, limitations, and possible evolution as a prognostic tool of DTI in spinal cord injury (SCI). For this systematic literature review, a detailed search was performed using PubMed (2005-2021), Cochrane Database of Systematic Reviews (2016-2021), and Cochrane Central Register of Controlled Trials (2016-2021). To be included, studies had to report the use of DTI in SCIs, its clinical relevance, and its use as a prognostic tool. We identified 17 studies comprising 299 patients. The mean age of patients was 41.22 ± 10.62 years. There was a prevalence of males (70.9%) compared with females (29.1%). The main spinal cord tract involved and studied in SCIs was the cervical tract (57.5%), followed by conus terminalis (15.4%) and dorsal tract (13.7%). In all studies based on American Spine Injury Association impairment scale score for neurological assessment, a correlation was found between FA values and American Spine Injury Association impairment scale: patients with complete SCI had a statistically significative lower FA value at the injured site compared with patients with incomplete SCI. Published clinical studies showed promising results for the utility of DTI parameters as noninvasive biomarkers in SCI grade evaluation, remaining an evolving area of further investigation.

White Cord Syndrome After Cervical or Thoracic Spinal Cord Decompression. Hemodynamic Complication or Mechanical Damage? An Underestimated Nosographic Entity.

The ischemia/reperfusion mechanism is believed to be responsible for parenchymal damage caused by temporary hypoperfusion and worsened by the subsequent attempt of reperfusion. This represents a true challenge for physicians of several fields, including neurosurgeons. A limited number of papers have shed the light on a rare pathologic condition that affects patients experiencing an unexplained neurologic deficit after spine surgery, the so-called "white cord syndrome." This entity is believed to be caused by an "ischemia/reperfusion" injury on the spinal cord, documented by a postoperative intramedullary hyperintensity on T2-weighted magnetic resonance imaging sequences. To date, the cases of white cord syndrome reported in literature mostly refer to cervical spine surgery. However, the analysis of several reviews focusing on spine surgery outcome suggests postoperative neurologic deficits of new onset could be charged to a mechanism of ischemia/reperfusion, even if the physiopathology of this event is seldom explored or at least discussed. The same neuroradiologic finding can suggest mechanical damage due to inappropriate surgical manipulation. On this purpose, we performed a systematic review of the literature with the aim to identify and analyze all the factors potentially contributing to ischemic/reperfusion damage of the spinal cord that may potentially complicate any spinal surgery, without distinction between cervical or thoracic segments. Finally, we believe that postoperative neurologic deficit after spinal surgery constituting the "white cord syndrome" could be under-reported; both neurosurgeons and patients should be fully aware of this rare but potentially devasting complication burdening cervical and thoracic spine surgery.

Intracranial Venous Alteration in Patients With Aneurysmal Subarachnoid Hemorrhage: Protocol for the Prospective and Observational SAH Multicenter Study (SMS).

Background: Arterial vasospasm has been ascribed as the responsible etiology of delayed cerebral infarction in patients with aneurysmal subarachnoid hemorrhage (aSAH), but other neurovascular structures may be involved. We present the protocol for a multicenter, prospective, observational study focused on analyzing morphological changes in cerebral veins of patients with aSAH. Methods and Analysis: In a retrospective arm, we will collect head arterial and venous CT angiograms (CTA) of 50 patients with aSAH and 50 matching healthy controls at days 0-2 and 7-10, comparing morphological venous changes. A multicenter prospective observational study will follow. Patients aged ≥18 years of any gender with aSAH will be enrolled at 9 participating centers based on the predetermined eligibility criteria. A sample size of 52 aSAH patients is expected, and 52 healthy controls matched per age, gender, and comorbidities will be identified. For each patient, sequential CTA will be conducted upon admission (day 0-2), at 7-10 days, and at 14-21 days after aSAH, evaluating volumes and morphology of the cerebral deep veins and main cortical veins. One specialized image collecting center will analyze all anonymized CTA scans, performing volumetric calculation of targeted veins. Morphological venous changes over time will be evaluated using the Dice coefficient and the Jaccard index and scored using the Boeckh-Behrens system. Morphological venous changes will be correlated to clinical outcomes and compared between patients with aSAH and healthy-controls, and among groups based on surgical/endovascular treatments for aSAH. Ethics and Dissemination: This protocol has been approved by the ethics committee and institutional review board of Ethikkommission, SALK, Salzburg, Austria, and will be approved at all participating sites. The study will comply with the Declaration of Helsinki. Written informed consent will be obtained from all enrolled patients or their legal tutors. We will present our findings at academic conferences and peer-reviewed journals. Approved Protocol Version and Registration: Version 2, 09 June 2021.

The Role of 3D-Printed Custom-Made Vertebral Body Implants in the Treatment of Spinal Tumors: A Systematic Review.

In spinal surgery, 3D prothesis represents a useful instrument for spinal reconstruction after the removal of spinal tumors that require an "en bloc" resection. This represents a complex and demanding procedure, aiming to restore spinal length, alignment and weight-bearing capacity and to provide immediate stability. Thus, in this systematic review the authors searched the literature to investigate and discuss the advantages and limitations of using 3D-printed custom-made vertebral bodies in the treatment of spinal tumors. A systematic literature review was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement, with no limits in terms of date of publication. The collected studies were exported to Mendeley. The articles were selected according to the following inclusion criteria: availability of full articles, full articles in English, studies regarding the implant of 3D custom-made prothesis after total or partial vertebral resection, studies regarding patients with a histologically confirmed diagnosis of primary spinal tumor or solitary bone metastasis; studies evaluating the implant of 3d custom-made prothesis in the cervical, thoracic, and lumbar spine. Nineteen published studies were included in this literature review, and include a total of 87 patients, 49 males (56.3%) and 38 females (43.7%). The main tumoral location and primary tumor diagnosis were evaluated. The 3D custom-made prothesis represents a feasible tool after tumor en-bloc resection in spinal reconstruction. This procedure is still evolving, and long-term follow-ups are mandatory to assess its safeness and usefulness.

Spinal Cord Stimulation to Treat Unresponsive Cancer Pain: A Possible Solution in Palliative Oncological Therapy.

(1) Background: Treatment of cancer-related pain is still challenging, and it can be managed by both medical and interventional therapies. Spinal Cord Stimulation (SCS) is a minimally invasive technique, and its use is rapidly increasing in the treatment of chronic pain. (2) Materials and Methods: Our study aims to perform a review of the pertinent literature about current evidences in cancer pain treatment by Spinal Cord Stimulation. Moreover, we created a database based on case reports or case series (18 studies) in the literature. We analyzed a clinical group of oncological patients affected by intractable pain undergoing SCS implantation, focusing on outcome. (3) Results: The analysis of the 18 included studies in our series has shown a reduction in painful symptoms in 48 out of 56 treated patients (87.51%); also 53 out of 56 patients (96.64%) have shown an improvement in their Quality of Life (QoL). (4) Conclusions: Spinal Cord Stimulation can be considered an efficient method in the treatment of cancer-related pain. However, literature regarding SCS for the treatment of cancer-related pain is largely represented by case reports and small case series, with no effective population studies or Randomized Controlled Trials demonstrating the efficacy and the level of evidence. Further prospective studies are needed.

The Palliative Care in the Metastatic Spinal Tumors. A Systematic Review on the Radiotherapy and Surgical Perspective.

Spine represents the most common site for metastatic disease involvement. Due to the close relationship between the spinal cord and critical structures, therapeutical management of metastatic spinal cord disease remains challenging. Spinal localization can lead to neurological sequelae, which can significantly affect the quality of life in patients with a limited life expectancy. The authors conducted a systematic literature review according to PRISMA guidelines in order to determine the impact of the most updated palliative care on spinal metastases. The initial literature search retrieved 2526 articles, manually screened based on detailed exclusion criteria. Finally, 65 studies met the inclusion criteria and were finally included in the systematic review. In the wide scenario of palliative care, nowadays, recent medical or surgical treatments represent valuable options for ameliorating pain and improving patients QoL in such this condition.