Anatomo-physiological basis and applied techniques of electrical neuromodulation in chronic pain.

Chronic pain, a complex and debilitating condition, poses a significant challenge to both patients and healthcare providers worldwide. Conventional pharmacological interventions often prove inadequate in delivering satisfactory relief while carrying the risks of addiction and adverse reactions. In recent years, electric neuromodulation emerged as a promising alternative in chronic pain management. This method entails the precise administration of electrical stimulation to specific nerves or regions within the central nervous system to regulate pain signals. Through mechanisms that include the alteration of neural activity and the release of endogenous pain-relieving substances, electric neuromodulation can effectively alleviate pain and improve patients' quality of life. Several modalities of electric neuromodulation, with a different grade of invasiveness, provide tailored strategies to tackle various forms and origins of chronic pain. Through an exploration of the anatomical and physiological pathways of chronic pain, encompassing neurotransmitter involvement, this narrative review offers insights into electrical therapies' mechanisms of action, clinical utility, and future perspectives in chronic pain management.

The "state of the art" of intraoperative neurophysiological monitoring: An Italian neurosurgical survey.

Introduction: Intraoperative Neurophysiological Monitoring (IOM) is widely used in neurosurgery but specific guidelines are lacking. Therefore, we can assume differences in IOM application between Neurosurgical centers. Research question: The section of Functional Neurosurgery of the Italian Society of Neurosurgery realized a survey aiming to obtain general data on the current practice of IOM in Italy. Materials and methods: A 22-item questionnaire was designed focusing on: volume procedures, indications, awake surgery, experience, organization and equipe. The questionnaire has been sent to Italian Neurosurgery centers. Results: A total of 54 centers completed the survey. The annual volume of surgeries range from 300 to 2000, and IOM is used in 10-20% of the procedures. In 46% of the cases is a neurologist or a neurophysiologist who performs IOM. For supra-tentorial pathology, almost all perform MEPs (94%) SSEPs (89%), direct cortical stimulation (85%). All centers perform IOM in spinal surgery and 95% in posterior fossa surgery. Among the 50% that perform peripheral nerve surgery, all use IOM. Awake surgery is performed by 70% of centers. The neurosurgeon is the only responsible for IOM in 35% of centers. In 83% of cases IOM implementation is adequate to the request. Discussion and conclusions: The Italian Neurosurgical centers perform IOM with high level of specialization, but differences exist in organization, techniques, and expertise. Our survey provides a snapshot of the state of the art in Italy and it could be a starting point to implement a consensus on the practice of IOM.

The Role of Treatment-Related Parameters and Brain Morphology in the Lesion Volume of Magnetic-Resonance-Guided Focused Ultrasound Thalamotomy in Patients with Tremor-Dominant Neurological Conditions.

PURPOSE: To determine the best predictor of lesion volume induced by magnetic resonance (MR)-guided focused ultrasound (MRgFUS) thalamotomy in patients with tremor-dominant symptoms in Parkinson's disease (PD) and essential tremor (ET) patients. METHODS: Thirty-six neurological patients with medication-refractory tremor (n°19 PD; n°17 ET) were treated using a commercial MRgFUS brain system (Exablate Neuro 4000, Insightec) integrated with a 1.5 T MRI unit (Sigma HDxt; GE Medical System). Linear regression analysis was used to determine how the demographic, clinical, radiological (Fazekas scale), volumetric (total GM/WM/CSF volume, cortical thickness), and MRgFUS-related parameters [Skull Density Ratio (SDR), n° of transducer elements, n° of sonications, skull area, maximal energy delivered (watt), maximal power delivered (joule), maximal sonication time delivered, maximal mean temperature reached (T°C_max), accumulated thermal dose (ATD)] impact on ventral intermediate (VIM)-thalamotomy-related 3D volumetric lesions of necrosis and edema. RESULTS: The VIM thalamotomy was clinically efficacious in improving the tremor symptoms of all the patients as measured at 1 week after treatment. Multiple regression analysis revealed that T°C_max and n° of transducer elements were the best predictors of the necrosis and edema volumes. Moreover, total WM volume also predicted the size of necrosis. CONCLUSIONS: Our study provides new insights into the clinical MRgFUS procedures that can be used to forecast brain lesion size and improve treatment outcomes.

A novel 3D anatomical visualization system to avoid injuries of nerves in retrosigmoid approach.

The retro-sigmoid approach (RA), widely used during different neurosurgical procedures, is burdened by the risk of injuries of the nerves that cross that region contributing to possible postoperative complications. By using, anatomage table (AT), a novel 3D anatomical visualization system, we described the nerves passing through the retromastoid area including the great occipital nerve (GON), the lesser occipital nerve (LON) and the great auricular nerve (GAN), and their courses from the origins, till terminal branches. Moreover, using dedicated software, we measured distances between the nerves and well-recognizable bony landmarks. After identifying the nerves and their distances from bony landmarks, we observed that the safest and risk-free skin incision should be made in an area delimited, superiorly from the superior nuchal line (or slightly higher), and inferiorly from a plane passing at 1-1.5 cm above the mastoid tip. The lateral aspect of such an area should not exceed 9.5-10 cm from the inion, while the medial one should be more than 7 cm far from the inion. This anatomical information has been useful in defining anatomical landmarks and reducing the risk of complications, mainly related to nerve injury, in RA. In-depth neuroanatomic knowledge of the cutaneous nerves of the retromastoid area is essential to minimize the complications related to their injury during different neurosurgical approaches. Our findings suggest that the AT is a reliable tool to enhance understanding of the anatomy, and thus contributing to the refinement of surgical techniques.

Primary Intracranial Gliosarcoma: Is It Really a Variant of Glioblastoma? An Update of the Clinical, Radiological, and Biomolecular Characteristics.

Gliosarcomas (GS) are sporadic malignant tumors classified as a Glioblastoma (GBM) variant with IDH-wild type phenotype. It appears as a well-circumscribed lesion with a biphasic, glial, and metaplastic mesenchymal component. The current knowledge about GS comes from the limited literature. Furthermore, recent studies describe peculiar characteristics of GS, such as hypothesizing that it could be a clinical-pathological entity different from GBM. Here, we review radiological, biomolecular, and clinical data to describe the peculiar characteristics of PGS, treatment options, and outcomes in light of the most recent literature. A comprehensive literature review of PubMed and Web of Science databases was conducted for articles written in English focused on gliosarcoma until 2023. We include relevant data from a few case series and only a single meta-analysis. Recent evidence describes peculiar characteristics of PGS, suggesting that it might be a specific clinical-pathological entity different from GBM. This review facilitates our understanding of this rare malignant brain tumor. However, in the future we recommend multi-center studies and large-scale metanalyses to clarify the biomolecular pathways of PGS to develop new specific therapeutic protocols, different from conventional GBM therapy in light of the new therapeutic opportunities.

The Role of Autopsy and Post-Mortem Investigations in Falling Traumas in the Hospital Environment.

Falls in a hospital setting are a global public health problem. Despite the production of sensors and various preventive tools to reduce the risk, falls remain a dangerous event with a significant impact on the morbidity and mortality of patients. Despite numerous prevention strategies, falling in the hospital are not always investigated and the autopsy is not always performed in these cases, so it is often not known whether the death is related to the fall or to other causes, inevitably affecting the assessment of any profiles of medical liability for health personnel or for the hospital in the accident. We describe three cases of falls that occurred in different hospitals, in which the autopsy allowed to diagnose with certainty the extent of the trauma and to reconstruct its dynamics. Along with the circumstantial and documentary analyses, deficiencies both in the trauma diagnostics and in the application of the safety measures on the patients were showed. Together with the description of our cases, we propose the post-mortem investigations of these events, both for judicial and risk management purposes.

Spinal Cord Stimulation in Chronic Low Back Pain Syndrome: Mechanisms of Modulation, Technical Features and Clinical Application.

Chronic low-back pain (CLBP) is a common disease with several negative consequences on the quality of life, work and activity ability and increased costs to the health-care system. When pharmacological, psychological, physical and occupational therapies or surgery fail to reduce CLBP, patients may be a candidate for Spinal Cord Stimulation (SCS). SCS consists of the transcutaneous or surgical implantation of different types of electrodes in the epidural space; electrodes are then connected to an Implanted Pulse Generator (IPG) that generates stimulating currents. Through spinal and supraspinal mechanisms based on the "gate control theory for pain transmission", SCS reduces symptoms of CLBP in the almost totality of well-selected patients and its effect lasts up to eight years in around 75% of patients. However, the evidence in favor of SCS still remains weak, mainly due to poor trial methodology and design. This narrative review is mainly addressed to those professionals that may encounter patients with CLBP failing conventional treatments. For this reason, we report the mechanisms of pain relief during SCS, the technical features and some clinical considerations about the application of SCS in patients with CLBP.

Deep brain stimulation for Parkinson's disease in practice: results of the survey by the Italian Neurosurgery Society.

BACKGROUND: Deep brain stimulation (DBS) is a safe and effective treatment for patients with advanced Parkinson's disease (PD) and many neurosurgical centers in Italy have a DBS program. Considering the prevalence of PD and criteria for DBS implantation, about 3200-10,350 PD patients may benefit from DBS in Italy. The global management of patients underwent DBS is complex and it can be supposed that many differences exist between centers in clinical practice. The Italian Neurosurgery Society (SINch) designed this survey to investigate the state of the art of DBS for PD in Italy. METHODS: A 26-item closed-ended question survey was designed and sanded by email at all Italian Neurosurgery centers. The main topic investigated was DBS teams, anatomical target selection, surgical procedure, neuroimaging, intraoperative target localization, DBS device and patients' follow-up. RESULTS: A total of 23 neurosurgery centers completed the survey. There are mainly low-to medium-volume centers (<20 annual DBS procedures) with dedicated DBS teams. The principal anatomical target used is subthalamic nucleus (STN) and, relative to the surgical technique, it emerges that in Italy DBS are bilaterally implanted in a single-step session with awake anesthesia and with frame-based technique. Final leads positioning is defined by microelectrode recordings (MER) and microstimulation (MS), with limited role of intraoperative neuroimaging (MRI and O-Arm). The stimulation is started at 15 or 30 days from procedure. CONCLUSIONS: Many centers of neurosurgery in Italy have a well-established DBS program for patients with advanced PD and some practical differences in technique between centers exist. Further investigation is needed to investigate specific criteria for selecting one technique over another.

Percutaneous intradiscal injection of radiopaque gelified ethanol: short- and long-term functional outcome and complication rate in a consecutive series of patients with lumbar disc herniation.

Lumbar disc herniation (LDH) is a common cause of low back pain (LBP) and/or radicular pain (RP). Over the years, different therapies have been proposed to treat symptomatic LDH, including different minimally invasive techniques and open surgical methods. Recently, percutaneous intradiscal injection of radiopaque gelified ethanol (RGE) DiscoGel® has emerged as an effective therapeutic option in patients with LDH. Nevertheless, only few studies addressed the reliability of this technique. The purpose of this study was to evaluate the efficacy and safety of this procedure. We analysed surgical and outcome data of patients with small or medium LDH treated by DiscoGel between 2012 to 2015. Outcome variables included pain relief, the limitation on physical activity and severity of depression status. Overall, complication rate was defined as the occurrence of any perioperative adverse events. A total of 94 consecutive patients were enrolled in the study. Pain relief was achieved in 90.6% and 88.8% of patients at 1- and 4-year follow-up, respectively. At the last follow-up, at least a satisfactory result was achieved in 92.5% of patients. Similar results were obtained in the limitation on physical activity. Depression status did not significantly change after treatment. There was no mortality, and no patients experienced permanent sequelae. In well-selected patients, DiscoGel has proved effective in maintaining excellent functional results in terms of pain relief and limitation on physical activity while minimizing the overall rate of complications related to these kinds of surgical procedures.

Deep brain stimulation for treatment-resistant depression: a safe and effective option.

Introduction: Major depressive disorder (MDD) is the leading cause of years lost to disability worldwide. Pharmacotherapy and psychotherapy are effective treatments in most depressive episodes; but, about 30% of MDD patients remain symptomatic, and relapse is a common event. Recently, deep brain stimulation (DBS) has emerged as a valid therapeutic option in treatment-resistant depression (TRD) patients.Areas covered: In this paper, the authors summarize the findings of studies focused on these pathophysiologic phenomena and specifically on the role of DBS as a therapeutic option in TRD patients. The authors simply reviewed RCTs, open-label studies, neurophysiological mechanisms of DBS in MDD, and the possible role of different targets. Finally, we suggest possible future options.Expert opinion: Depression is a systems-level disorder, involving several brain structures. Neuroimaging studies demonstrate multiple interconnected regions that modulate different neural networks. DBS can modulate different targets, and others are under investigation. Among these subcallosal cingulate gyrus (SCG), ventral capsule and ventral striatum (VC/VS) seems to be the most relevant targets. We believe that, in the next future, DBS for TRD might become a first-line of treatment, especially using directional leads, that may help us to improve therapeutic effects.

A Novel Technical Refinement of Microvascular Decompression: Pain Relief and Complication Rate in a Consecutive Series of Patients With Trigeminal Neuralgia.

BACKGROUND: Microvascular decompression (MVD) represents a milestone for the treatment of trigeminal neuralgia (TN). Nevertheless, several complications still occur and may negatively affect the outcome. We recently proposed some technical nuances for complication avoidance related to MVD. OBJECTIVE: To verify the efficacy of the proposed refinement of the standard MVD technique in terms of resolution of the pain and reduction of complication rates. METHODS: We analyzed surgical and outcome data of patients with TN using a novel surgical refinement to MVD, over the last 4 yr. Outcome variables included pain relief, facial numbness, muscular atrophy, local cutaneous occipital and temporal pain or numbness, cerebellar injury, hearing loss, cranial nerve deficits, wound infection, and cerebrospinal fluid (CSF) leak. Overall complication rate was defined as the occurrence of any of the aforementioned items. RESULTS: A total of 72 consecutive patients were enrolled in the study. Pain relief was achieved in 91.6% and 88.8% of patients at 1- and 4-yr follow-up, respectively. No patient reported postoperative facial numbness during the entire follow-up period. The incidence of CSF leak was 1.4%. One patient developed a complete hearing loss and another a minor cerebellar ischemia. There was no mortality. The overall complication rate was 5.6%, but only 1.4% of patients experienced permanent sequelae. CONCLUSION: The proposed refinement of the standard MVD technique has proved effective in maintaining excellent results in terms of pain relief while minimizing the overall complication rate associated with this surgical approach.

Impact of [64Cu][Cu(ATSM)] PET/CT in the evaluation of hypoxia in a patient with Glioblastoma: a case report.

BACKGROUND: Glioblastoma multiform (GBM), a malignant brain tumour, has a very often poor prognosis. The therapeutic approach is represented by surgery followed by radiotherapy and chemotherapy. Hypoxia is a factor that causes a reduction of both radiotherapy and chemotherapy effectiveness in GBM and other cancers. Through the use of [64Cu][Cu(ATSM)], a hypoxia-targeting positron emission tomography (PET) radiotracer, is possible to identify the presence of hypoxic areas within a lesion and therefore modulate the therapeutic approach according to the findings. CASE PRESENTATION: In this case report, we observed an increase of radiotracer uptake from early acquisition to late acquisition in hypoxia sites and high correlation between [64Cu][Cu(ATSM) PET/CT results and expression of the hypoxia marker HIF-1α. CONCLUSIONS: [64Cu][Cu(ATSM) PET/CT represents a valid opportunity to reveal in vivo hypoxic areas in GBM lesion which can guide clinicians on selecting GMB patient's therapeutic scheme.

Suspected Pulmonary Embolism after Oxygen-Ozone Therapy for Low Back Pain.

Oxygen-ozone therapy is used to treat degenerative pathology of the spine when surgery is not needed (e.g., removal of a herniated disk). Some authors have described it as a safe and effective procedure in ∼ 70 to 90% of patients. The aim of the therapy is to dehydrate the intervertebral disk and alter its contents. However, this treatment has been associated with some rare but very serious side effects. Both cardiac damage and a case of fulminant septicemia were reported. We describe a case of suspected pulmonary embolism, followed by sudden death, in an elderly woman treated with oxygen-ozone therapy for lumbar pain caused by disk protrusion. We believe a massive pulmonary embolism occurred, probably caused by an intradiskal injection that accidentally punctured a venous vessel and created emboli.

Occipitocervical Fusion.

Occipitocervical fusion is a surgical technique in continuous evolution due to the innovation of devices, operative and instrumentation techniques. The aetiologies responsible for occipitocervical instability are trauma, neoplastic disease, metabolic disease or congenital disease. A variety of stabilization techniques are currently available depending on the type of patient and surgeon's experience. Each of these techniques requires thorough knowledge of the anatomy of the craniovertebral junction.

Occipital Nerve Stimulation for Refractory Pain after Occipitocervical Fusion.

Occipital nerve stimulation (ONS) is electric stimulation of the distal branches of the greater occipital nerve by cylindrical or paddle leads implanted in subcutaneous occipital tissue. This surgical option has emerged as a promising treatment for different types of disabling medical refractory headache and recently also for residual occipital and nuchal pain after previous occipitocervical fusion. The mechanisms of action have not yet been clearly explained: electrical stimulation of the occipital nerve has both peripheral and central effects on the nervous system, which may modulate nociception. ONS is a well-tolerated and safe procedure in comparison with other invasive modalities of treatment. Lead migration/dislodgement is a common complication, but use of new surgical techniques and leads may reduce the rate of this complication.

Von Hippel-Lindau disease: when neurosurgery meets nephrology, ophthalmology and genetics.

INTRODUCTION: Von Hippel-Lindau (VHL) disease is a dominantly inherited condition associated with tumors in multiple organs, whose treatment requires heightened multidisciplinary teamwork. Therefore, a document summarizing all the pertinent knowledge is needed to enhance coordination of care. EVIDENCE ACQUISITION: A systematic review of the literature from the Medline, Embase and Cochrane Central databases was performed. From 1970 to 2017, all articles meeting specific inclusion criteria were included by at least one specialist physician for each field. EVIDENCE SYNTHESIS: We included 95 articles, mostly dealing with genetics or management of VHL associated tumors in one organ system. There were no papers discussing the manifestations of VHL altogether, which was the aim of our paper. CONCLUSIONS: VHL requires a multidisciplinary management to provide the highest quality of care. Coordination and communication between patients and caregivers is enhanced when knowledge is shared. Gathering together specialists in different domains around the production and reading of a comprehensive document such as the one hereby may contribute to this purpose.

Cervical spinal cord compression from delayed epidural scar tissue formation around plate lead for SCS.

Cervical spinal compression is a serious and rare complication of spinal cord stimulation (SCS) that can occur using leads placed via open surgical approach. The present report describe a case of cervical plate lead implant that developed spinal and radicular compression symptoms after seven years due to the growth of fibrotic epidural mass at the level of lead. A review of literature is provided. A 59-year­old woman with 3-year history of left arm post­traumatic complex regional pain syndrome (CRPS) was treated with SCS performed with the implant of paddle lead in the epidural space from C3-C5. Seven years later she reported progressive paresthesia along the spine and the limbs, gait ataxia with sensation of weakness in the legs, increased muscle tone and tendon reflexes in the lower extremities and decrease in effectiveness of stimulation. Cervical CT showed a tissue mass into the cervical canal posteriorly to the lead. This finding was confirmed by MR performed after lead removal that also allowed to document the amount of spinal cord compression. The patient underwent C4-C5-C6 laminectomy and a thick scar was removed from the dura. After surgery there was progressive and incomplete improvement of neurological signs but symptoms related to algodystrophy recurred partly. The formation of hypertrophic epidural scar tissue at the level of lead implant must be taken into consideration in presence of the onset of progressive cervical myelopathy in patient treated with SCS using laminectomy lead.

A Novel Diagnostic and Prognostic Tool for Simple Decompression of Ulnar Nerve in Cubital Tunnel Syndrome.

BACKGROUND: Surgical decompression of the ulnar nerve (UN) is effective for treating cubital tunnel syndrome (CubTS). Nevertheless, the outcome is not always satisfying. Different surgical, clinical, and imaging findings have been claimed as outcome predictors, but there is no consensus in the literature. We analyzed the outcome-predicting role of ultrasonography (US) of the UN in patients with CubTS and its possible role for diagnosis and follow-up. METHODS: Patients with CubTS treated by simple UN decompression underwent US and electrodiagnotic (ED) studies of the UN at the elbow before and after surgery. Outcome was evaluated through the Bishop scale. A correlation analysis between pre- and postoperative clinical, US, and ED findings was performed. RESULTS: Thirty-six patients were enrolled. Preoperatively, we observed a negative correlation between the motor conduction velocity (MCV) and the transverse (TD) and anteroposterior diameters and cross-sectional area (CSA) of the UN at the precubital (P = 0.001, P = 0.001, P = 0.005) and cubital level (P = 0.02, P = 0.002, P = 0.001). Preoperative precubital TD and CSA were associated with outcome (P = 0.01, P = 0.006) and postoperative MCV (P = 0.004, P = 0.008). The cut-off values TD >6 mm and CSA >23.91 mm2 were predictors of poor outcome. Finally, postoperative cubital TD and CSA values were inversely correlated with outcome (P = 0.0002, P = 0.0007) and postoperative MCV (P = 0.0002, P = 0.0004). CONCLUSIONS: The US examination of the UN is useful for the management of patients with CubTS as an adjunct to clinical and ED evaluations. US measurements are correlated with pre- and postoperative ED findings and thus are useful for diagnosis and follow-up. Interestingly, specific precubital US measurements are good predictors of outcome.