Integrative approaches in spinal cord stimulation: Neuropathic pain management and motor recovery in spinal cord injury. A narrative review.

Introduction: Spinal cord stimulation is a widespread treatment of chronic neuropathic pain from different conditions. Several novel and improving technologies have been recently developed to increase the effect of neuromodulation in patients refractory to pharmacological therapy. Research question: To explore spinal cord stimulation's mechanisms of action, indications, and management. Material and methods: The paper initially explores the mechanism of action of this procedure based on the generation of an electric field between electrodes placed on the posterior dural surface of the spinal cord probably interfering with the transmission of pain stimuli to the brain. Subsequently, the most consolidated criteria for selecting patients for surgery, which constitute a major issue of debate, were defined. Thereafter, the fundamental patterns of stimulation were summarized by exploring the advantages and side effects. Lastly, the most common side effects and the related management were discussed. Results: Proper selection of the patient is of paramount importance to achieve the best results from this specific neuromodulation treatment. Regarding the different types of stimulation patterns, no definite evidence-based guidelines exist on the most appropriate approach in relation to the specific type of neuropathic pain. Both burst stimulation and high-frequency stimulation are innovative techniques that reduce the risk of paresthesias compared with conventional stimulation. Discussion and conclusion: Novel protocols of stimulation (burst stimulation and high frequency stimulation) may improve the trade-off between therapeutic benefits and potential side effects. Likewise, decreasing the rates of hardware-related complications will be also useful to increase the application of neuromodulation in clinical settings.

Proposal of a new score system (Cervical Surgical Score) for management of degenerative cervical myelopathy.

BACKGROUND: To date, no shared algorithms with the aim of guiding surgical strategy in complex cases of degenerative cervical myelopathy (DCM) exist. Our purpose is to present the Cervical Surgical Score (CSS) which could help in identifying complex DCM cases, suggesting a surgical strategy. METHODS: We created the CSS based on multidisciplinary and literature-focused discussions, based on eight parameters including number of levels of cervical pathology and myelopathy, type and predominance of compression and grade of clinical myelopathy. We prospectively enrolled surgical DCM patients in a 15-months period, collecting clinical and radiological data. During outpatient clinic a specific surgical indication was offered to DCM patients. To validate the score, each outpatient clinic surgical indication was compared a posteriori to the one that resulted from multidisciplinary CSS scoring, focusing on patients for which both an anterior and posterior approach were considered suitable. RESULTS: A total of 100 patients operated on for DCM at our Institution between December 2021 and February 2023 were prospectively enrolled. In 53% of patients the pathology was present at more than two levels. According to CSS calculation, 14% of patients resulted in the "grey zone", where both an anterior and posterior approach were deemed feasible. Among them, in 42.8% of cases the CSS allowed a modification of the originally planned surgery. Looking at outcome, an improvement of m-JOA score in 62% of patients was disclosed. CONCLUSIONS: This preliminary study showed the reliability and usefulness of CSS in detecting complex DCM cases, requiring further analysis by expert spine surgeons, suggesting a surgical strategy.

Posterior Hypothalamic Region Deep Brain Stimulation for the Treatment of Aggression Disorders in Patients with Intellectual Disability: A Systematic Review.

INTRODUCTION: Aggressive disorders, in patients with intellectual disability, are satisfactorily managed with an educational, psychological, and pharmacological approach. Posterior hypothalamic region deep brain stimulation emerged in the last two decades as a promising treatment for patients with severe aggressive disorders. However, limited experiences are reported in the literature. METHODS: A systematic review was performed following PRISMA guidelines and recommendations by querying PubMed and Embase on August 24th, 2022, with the ensuing string parameters: ([deep brain stimulation] OR [DBS]) AND ([aggressiv*] OR disruptive). Cochrane Library, DynaMed, and ClinicalTrials.gov were consulted using the combination of keywords "deep brain stimulation" and "aggressive" or "aggression". The clinical outcome at the last follow-up and the rate of complications were considered primary and secondary outcomes of interest. RESULTS: The initial search identified 1,080 records, but only 10 studies met the inclusion criteria and were considered. The analysis of clinical outcome and complications was therefore performed on a total of 60 patients. Quality of all selected studies was classified as high, but one. Mean Overt Aggression Scale (OAS) improvement was 68%, while Inventory for Client Agency Planning (ICAP) improvement ranged between 38.3% and 80%. Complications occurred in 4 patients (6.7%). CONCLUSION: Posterior hypothalamic region deep brain stimulation may be considered a valuable option for patients with severe aggression disorders and ID. This review can represent a mainstay for those who will be engaged in the surgical treatment of these patients.

Microvascular decompression for trigeminal neuralgia: a single-center experience with 516 cases, including 32 patients with multiple sclerosis.

BACKGROUND AND OBJECTIVES: To evaluate the effectiveness and long-term pain relief of microvascular decompression (MVD) for "typical" trigeminal neuralgia (TN), including patients affected by multiple sclerosis (MS). METHODS: Between January 2011 and December 2022, 516 consecutive patients presenting with trigeminal neuralgia and a diagnosed neurovascular conflict at MRI underwent microvascular decompression surgery in our neurosurgery department. Ten surgeons with different ages and experiences performed the surgical procedures. Pain improvement, re-operation rate, and complication rates were retrospectively collected and analyzed. RESULTS: 516 patients were included (214 males 302 females, ranging from 12 to 87 years), including 32 patients with multiple sclerosis. Neurovascular compression was found in all cases during surgery. Barrow Neurological Institute pain intensity scale with a score of I was achieved in 404 patients (78,29%), a score II or III was obtained in 100 cases (19,37%) and a score of IV and V in 12 patients (2,32%). In the multiple sclerosis subset of patients, a BNI score of I was achieved in 21/32 (65.62%). The pain recurrence rate of our series was 15.11%. The follow-up for all patients was at least of 13 months, with a mean follow-up of 41.93 months (± 17.75 months, range 13-91 months). Neither intraoperative mortality nor major intra-operative complications occurred in the analyzed series. The re-operation rate was 12.98%. Thermorhizotomy, percutaneous balloon compression, cyber-knife radiosurgery, or new MVD were the surgical techniques utilized for re-operations. CONCLUSIONS: MVD may be considered an effective and safe surgical technique for TN, and in patients affected by multiple sclerosis, it may be proposed even if a less favorable outcome has to be expected with respect to classic TN patients. Larger studies focusing on the relation of multiple sclerosis with neurovascular compression are required.

3D4K exoscope in epilepsy surgery: a seminal experience.

BACKGROUND AND OBJECTIVES: To report the progressive introduction of the exoscope (EX) from surface lesionectomy to antero-mesial temporal lobectomy (AMTL) in an epilepsy surgery practice. METHODS: We describe a population of ten consecutive patients undergoing EX surgery, with a minimum follow-up of 6 months, that was compared to a similar population of patients referred to operative microscopic surgery (OM). RESULTS: All surgeries were performed with the use of EX or OM alone. Transient neurological complications for surgery in eloquent regions were recorded in one patient for each population. Nine and seven patients undergoing, respectively, EX and OM surgery resulted in Engel class Ia (90% vs. 70%). The mean duration of EX and OM surgery resulted in 265.5 and 237.9 min, respectively, with a mean of 308.3 and 253.3 min for AMTL cases, respectively. CONCLUSIONS: This preliminary study revealed that ORBEYE EX can be safe and effective in different types of epilepsy surgeries. The transition from OM to EX is fast, even though it is slower for the more challenging mesial temporal structure removal. Ergonomic and operative team interaction is improved by the use of EX. Our data need to be confirmed by larger studies.

Incidence and management of idiopathic peri-lead edema (IPLE) following deep brain stimulation (DBS) surgery: Case series and review of the literature.

OBJECTIVE: Idiopathic peri-lead edema (IPLE) is being increasingly described as a potential complication occurring after DBS surgery. Its incidence and relationship to post-operative symptoms, though, are still poorly defined and its understanding and management yet limited. METHODS: We reviewed delayed (≥ 72 h) post-operative CT imaging of patients who underwent DBS surgery at our Institution. A comparison of clinical and laboratory findings was carried out between patients with IPLE and controls. RESULTS: 61 patients, accounting for 115 electrodes, were included. Incidence of IPLE was 37.7 % per patient and 29.5 % per electrode. Patients with IPLE were significantly older than controls (52.82 ± 15.65 years vs 44.73 ± 18.82 years, p = 0.04). There was no difference in incidence of new-onset neurological symptoms between patients with IPLE and controls. Longer operative time (180.65 ± 34.30 min vs 158.34 ± 49.28 min, p = 0.06) and a greater number of MERs per electrode were associated with IPLE (3.37 ± 1.21 vs 3.00 ± 1.63, p = 0.089), though these comparisons did not meet the statistical significance. None of the patients with IPLE underwent hardware removal, with IPLE vanishing spontaneously over months. CONCLUSIONS: IPLE is an underestimated, benign event that may occur after DBS surgery. Age, longer operative time and MER use may represent risk factors for IPLE formation, but further studies are needed. The presence of post-operative neurological symptoms and fever was not associated with IPLE presence, highlighting its benign nature and suggesting that empiric treatment may not be always justified.

Fast and versatile platform for pedicle screw insertion planning.

PURPOSE: Computer-assisted surgical planning methods help to reduce the risks and costs in transpedicular fixation surgeries. However, most methods do not consider the speed and versatility of the planning as factors that improve its overall performance. In this work, we propose a method able to generate surgical plans in minimal time, within the required safety margins and accounting for the surgeon's personal preferences. METHODS: The proposed planning module takes as input a CT image of the patient, initial-guess insertion trajectories provided by the surgeon and a reduced set of parameters, delivering optimal screw sizes and trajectories in a very reduced time frame. RESULTS: The planning results were validated with quantitative metrics and feedback from surgeons. The whole planning pipeline can be executed at an estimated time of less than 1 min per vertebra. The surgeons remarked that the proposed trajectories remained in the safe area of the vertebra, and a Gertzbein-Robbins ranking of A or B was obtained for 95 % of them. CONCLUSIONS: The planning algorithm is safe and fast enough to perform in both pre-operative and intra-operative scenarios. Future steps will include the improvement of the preprocessing efficiency, as well as consideration of the spine's biomechanics and intervertebral rod constraints to improve the performance of the optimisation algorithm.

Left Mesial Temporooccipital PLNTY: Supracerebellar Transtentorial Approach in Epilepsy Surgery.

The supracerebellar transtentorial approach for the resection of brain lesion at the level of the mesial temporooccipital region is underused in the field of epilepsy surgery, despite the theoretical advantage of sparing normal brain structures, in particular in the dominant hemisphere for language. Hereby we present the case of a patient with a low-grade epilepsy associated tumor, presenting with weekly drug-resistant focal seizures, treated by a supracerebellar transtentorial lesionectomy. Surgery was uneventful and the histopathology revealed a pleomorphic low-grade neuroepithelial tumor of the young patient. At the 6-month follow-up, the patient did not present neurologic deficits and she never presented with seizures after surgery, so antiepileptic drug tapering started. The integration of supracerebellar transtentorial approach in the "armory" of the epilepsy neurosurgeon requires a dedicated expertise and an anesthesiologic setting used to manage the semisitting position; on the other hand, it could provide a relevant option to provide safe and complete lesionectomy in the mesial temporooccipital region, together with the more classical sublobar and transcerebral approaches (Video 1).

Vanishing contrast-enhancing peri-lead oedema following deep brain stimulation surgery: A case report.

Idiopathic peri-lead oedema (IPLE) after deep brain stimulation (DBS) surgery is still a poorly understood phenomenon. It is usually asymptomatic and does not present contrast enhancement at the post-operative Magnetic Resonance Imaging (MRI). Here we present the rare case of contrast-enhancing IPLE occurring in a completely asymptomatic patient vanishing spontaneously at the radiological follow-up at one month. The radiological picture raised the concerns of peri-lead abscess, but the absence of clinical and laboratory signs of infection and the benefit of DBS over the patient's dystonic symptoms prompted a more conservative approach. To our knowledge, this is the first reported case of asymptomatic contrast-enhancing IPLE conservatively managed.

Assessing the role of sodium fluorescein in peripheral nerve sheath tumors and mimicking lesions surgery: An update after 142 cases.

Objective: Peripheral nerve sheath tumors (PNST) include mainly schwannomas and neurofibromas. Surgical resection represents the mainstay of treatment but due to their pathogenesis, distinguishing between intact functional nerve and the fibers from whence the PNST arose may not always be easy to perform, constituting the most relevant risk factor in determining a worsening in neurological condition. The introduction of intraoperative tools to better visualize these tumors could help achieve a gross-total resection. In this study, we analyzed the effect of sodium fluorescein (SF) on the visualization and resection of a large cohort of PNST. Methods: Between September 2018 and December 2021, 142 consecutive patients harboring a suspected PNST underwent fluorescein-guided surgery at the Department of Neurosurgery of the Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. All patients presented with a different degree of contrast enhancement at preoperative MRI. SF was intravenously injected after intubation at 1 mg/kg. Intraoperative fluorescein characteristics and postoperative neurological and radiological outcomes were collected, analyzed, and retrospectively compared with a historical series. Results: 142 patients were included (42 syndromic and 100 sporadic); schwannoma was the predominant histology, followed by neurofibroma (17 neurofibroma e 12 plexiform neurofibroma) and MPNST. Bright fluorescence was present in all cases of schwannomas and neurofibromas, although with a less homogeneous pattern, whereas it was significantly less evident for malignant PNST; perineurioma and hybrid nerve sheath tumors were characterized by a faint fluorescence enhancement. The surgical resection rate in the general population and even among the subgroups was about 66.7%; from the comparative analysis, we found a consistently higher rate of complete tumor removal in plexiform neurofibromas, 66% in the "fluorescent" group vs 44% in the "historical" group (p-value < 0.05). The rate of complications and mean surgical time were superimposable among the two populations. Conclusions: SF is a valuable method for safe fluorescence-guided PNST and mimicking lesions resection. Our data showed a positive effect of fluorescein-guided surgery in increasing the rate of surgical resection of plexiform neurofibromas, suggesting a possible role in improving the functional and oncological outcome of these lesions.

Economic complexity and fertility: insights from a low fertility country.

This paper analyzes the relationship between a new indicator of economic context, economic complexity (EC), and fertility change in Italian provinces between 2006 and 2015. We hypothesize that the level of EC is associated with fertility as it reflects a territory's capacity to innovate, grow and create job opportunities. The results illustrate a clear positive association between EC and fertility change across Italian provinces for the period considered, net of traditional fertility predictors. Those areas that stand at the frontiers of EC are also more likely to dominate and adapt to the negative consequences of globalization.

The Lipid Asset Is Unbalanced in Peripheral Nerve Sheath Tumors.

Peripheral nerve sheath tumors (PNSTs) include schwannomas, neurofibromas (NFs), and plexiform neurofibromas (PNFs), among others. While they are benign tumors, according to their biological behavior, some have the potential for malignant degeneration, mainly PNFs. The specific factors contributing to the more aggressive behavior of some PNSTs compared to others are not precisely known. Considering that lipid homeostasis plays a crucial role in fibrotic/inflammatory processes and in several cancers, we hypothesized that the lipid asset was also unbalanced in this group of nerve tumors. Through untargeted lipidomics, NFs presented a significant increase in ceramide, phosphatidylcholine, and Vitamin A ester. PNFs displayed a marked decrease in 34 out of 50 lipid class analyzed. An increased level of ether- and oxidized-triacylglycerols was observed; phosphatidylcholines were reduced. After sphingolipidomic analysis, we observed six sphingolipid classes. Ceramide and dihydroceramides were statistically increased in NFs. All the glycosylated species appeared reduced in NFs, but increased in PNFs. Our findings suggested that different subtypes of PNSTs presented a specific modulation in the lipidic profile. The untargeted and targeted lipidomic approaches, which were not applied until now, contribute to better clarifying bioactive lipid roles in PNS natural history to highlight disease molecular features and pathogenesis.