Background: Ziconotide is an intrathecal drug administered for the treatment of chronic pain. The current literature lacks an exhaustive benefit/risk assessment on this drug. We herein focus on Ziconotide’s pharmacology and clinical applications. Methods: Literature research was conducted to identify studies on Ziconotide administration for the treatment of chronic pain, published between January 1990 and March 2023 and located via PubMed, Embase, Medline, Cinahl, and Web of Science, using the following keywords: Ziconotide, Omega conotoxin, Prialt, SNX-111, intrathecal therapy, and neuropathic pain. Only publications written in English were selected. Results: Among the 86 selected studies, we found 4 Randomized Controlled Trials (RCTs) and 3 prospective long-term studies concerning the intrathecal use of Ziconotide as a monotherapy in chronic pain. Other studies described the intrathecal infusion of Ziconotide combined with other drugs. Overall, Ziconotide has been proved to have strong efficacy for relieving chronic pain, although patients with co-morbid psychiatric disorders require a careful monitoring when treated with Ziconotide. Conclusions: Overall, the use of Ziconotide, as a monotherapy or in conjunction with other therapies for the treatment of chronic pain, was reported to be efficacious. Overall, its use in patients with chronic pain refractory to other pharmacologic agents outweighs the possible adverse consequences, thus resulting in a favorable benefit/risk assessment.

Objective: Pilocytic astrocytomas (PAs) are relatively benign tumors, usually enhancing on post-contrast MRI and often characterized by a mural nodule within a cystic component. Surgical resection represents the mainstay of treatment, and extent of resection (EOR) is associated with improved survival. In this study, we analyzed the effect of sodium fluorescein (SF) on the visualization and resection of these circumscribed astrocytic gliomas.Methods: Surgical databases at two neurosurgical departments (Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy and Department of Neurosurgery, University Medical Center Regensburg, Regensburg, Germany) were retrospectively reviewed to identify the cohort of patients with pilocytic astrocytoma who had undergone fluorescein-guided tumor resection at any of the centers between March 2016 and February 2022. SF was intravenously injected (5 mg/kg) immediately after the induction of general anesthesia. Tumors were removed using a microsurgical technique with the YELLOW 560 filter (Carl Zeiss Meditec, Oberkochen, Germany).Results: Forty-four patients (25 males and 19 females; 26 pediatric patients, mean age of 9.77 years, range 2 to 17 years; and 18 adult patients, mean age of 34.39 years, range 18 to 58 years) underwent fluorescein-guided surgery. No side effects related to SF occurred. In all tumors, contrast enhancement on preoperative MRI was correlated with intense, heterogeneous yellow fluorescence with bright fluorescent cystic fluid. Fluorescein was considered helpful in distinguishing tumors from viable tissue in all cases except three patients due to faint fluorescein enhancement. Biopsy was intended in two operations, and partial resection was intended in three operations. Gross total resection was achieved in 24 cases out of 39 patients scheduled for tumor removal (61.54%), in five cases a minimal residual volume was highlighted by postoperative MRI despite the intraoperative subjective evaluation of complete tumor removal (12.82%); in the other 10 cases, the resection was subtotal with fluorescent residual spots to avoid neurological worsening (25.64%).Conclusions: The use of SF is a valuable method for safe fluorescence-guided tumor resection. Our data showed a positive effect of fluorescein-guided surgery on intraoperative visualization during resection of Pas, suggesting a possible role in improving the extent of resection of these lesions.

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. To explore spinal cord stimulation’s mechanisms of action, indications, and management. 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. 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. 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.

Glioblastoma is a fast‐growing and aggressive form of brain cancer. Even with maximal treatment, patients show a low median survival and are often subjected to a high recurrence incidence. The currently available treatments require multimodal management, including maximal safe surgical resection, followed by radiation and chemotherapy. Because of the infiltrative glioblastoma nature, intraoperative differentiation of cancer tissue from normal brain parenchyma is very challenging, and this accounts for the low rate of complete tumor resection. For these reasons, clinicians have increasingly used various intraoperative adjuncts to improve surgical results, such as fluorescent agents. However, most of the existing fluorophores show several limitations such as poor selectivity, photostability, photosensitization and high costs. This could limit their application to successfully improve glioblastoma resection. In the present perspective, we highlight the possibility to develop next‐generation fluorescent tools able to more selectively label cancer cells during surgical resection.

It is commonly reported that maximizing surgical resection of contrast-enhancing regions in patients with glioblastoma improves overall survival. Efforts to achieve an improved rate of resection have included several tools: among those, the recent widespread of fluorophores. Sodium fluorescein is an unspecific, vascular dye which tends to accumulate in areas with an altered blood–brain barrier. In this retrospective analysis of patients prospectively enrolled in the FLUOCERTUM study, we aimed to assess the role of fluorescein-guided surgery on surgical radicality, survival, and morbidity. A retrospective review based on 93 consecutively and prospectively enrolled IDH wild-type glioblastoma patients (2016–2022) was performed; fluorescence characteristics, rate of resection, clinical outcome, and survival were analyzed. No side effect related to fluorescein occurred; all of the tumors presented a strong yellow-green enhancement and fluorescein was judged fundamental in distinguishing tumors from viable tissue in all cases. Gross total resection was achieved in 77 cases out of 93 patients (82.8%). After a mean follow-up time of 17.4 months (3–78 months), the median progression-free survival was 12 months, with a PFS-6 and PFS-12 of 94.2% and 50%, respectively, whereas median overall survival was estimated to be 16 months; survival at 6, 12, and 24 months was 91.8%, 72.3%, and 30.1%, respectively. Based on these results, we can assert that the fluorescein-guided technique is a safe and valuable method for patients harboring a newly diagnosed, untreated glioblastoma.