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.

A Benefit/Risk Assessment of Intrathecal Ziconotide in Chronic Pain: A Narrative Review.

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.

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.

Exoscopic-assisted posterior approach for the removal of thoracic dumbbell schwannoma: Three-dimensional operative video.

"Dumbbell" tumors are described as benign neoplasms presenting both intraspinal and extraspinal extensions, connected through the intervertebral foramen (McCormick, 1996) [1]. About 90 % of such tumors are histologically classified as schwannomas that most frequently arise in the thoracic region (Takamura and et al., 1997) [2]. Diagnosis is usually achieved as soon as the dimensional increase of the intracanal portion results in nerve or spinal cord compression (Ishikawa and et al., 2002) [3]. How to obtain a complete surgical resection of tumors with large or ventrally located extraforaminal components with a minimally invasive approach is still debated (Payer and et al., 2006) [4]. The single-stage posterior removal of the tumor is the most performed approach for lesions presenting with a small extra-foraminal component (Payer and et al., 2006) [4]. However, due to the reduced visual surgical field and poor control of the surrounding structures that could be obtained with an operative microscopic (OM) view, the application of this approach still appears to be limited to lesions with a large extraspinal component. An alternative surgical approach is the lateral transthoracic transpleural approach, which, however, carries greater risks of complications and often requires assistance from a thoracic surgeon. During the last decade, the exoscope was developed as a hybrid optical instrument, standing between the OM and the endoscope, merging the pros and cons of both visualization technologies, providing a wide viewing angle, high-resolution images, and non-monoaxial view. In this work we present a case of a 60-years old male patient with a 6-month history of dorsal pain and mild left limb paresthesia resistant to conservative treatment in which for the first time a single stage exoscopic-assisted (Olympus ORBEYE 4K-3D exoscope) posterior approach was used to remove entirely a thoracic dumbbell schwannoma with large extraspinal involvement.

The Application of Sodium Fluorescein in Resection of Medulloblastoma Under YELLOW 560 Filter: Feasibility and Preliminary Results of a Monocentric Cohort and Systematic Review.

BACKGROUND: Maximizing surgical resection of medulloblastoma (MB) affects overall survival; nevertheless, surgical resection remains a because of the infiltrative behavior of this tumor. Several dyes have been tested for improving tumor visualization; however, few reports with different protocols of fluorophores use are available and the results are inconsistent. Hence, we report our experience with sodium fluorescein in MB surgery, aiming to assess the role of this technique on the extent of resection. Furthermore, we performed a literature review of this topic. METHODS: Fluorescence characteristics, extent of resection, and clinical outcome were analyzed in 9 consecutively operated patients with MB. A comprehensive literature search and review for English-language articles concerning fluorescein application in MB was conducted. RESULTS: In our cohort, no side effect related to fluorescein occurred; all tumors presented with an intense or moderate yellow-green enhancement, and fluorescein was judged fundamental in distinguishing tumors from viable tissue in 7 of 9 cases. Gross total resection or near-total resection (i.e., a residual tumor volume <1.5 cm3) was achieved in 8 patients. The review explored the different techniques and surgical interpretations as well as surgical radicality; we did not find a homogenous protocol for fluorescein injection in the published articles. Fluorescence appeared moderate or intense in almost all cases, with a high percentage of usefulness and consensual achievement of a high rate of gross total resection. CONCLUSIONS: Based on these results, we can infer that fluorescein-guided surgical resection is a safe and valuable method for patients with MB.

What have we learned in fluorescein-guided resection of brain metastases? An update after 79 consecutive cases.

BACKGROUND: Cerebral metastasis (CM) is the most common malignancy affecting the brain. Individualized treatment of CM still represents a challenge for neuro-oncological teams: in patient eligible for surgery, complete tumor removal is the most relevant predictor of overall survival (OS) and neurological outcome. The development of surgical microscopes harboring specific filter able to elicit the fluorescent response from sodium fluorescein (SF) has facilitated fluorescein-guided microsurgery and the identification of pathological tumor tissue, especially at the tumor margins. In this study, we analyzed the effect of SF on the visualization and resection of a large monoinstitutional cohort of CM. METHODS: Surgical database of FLUOCERTUM study (Besta Institute, Milan, Italy) was retrospectively reviewed to find CM surgically removed with a fluorescein-guided technique from March 2016 to December 2022. SF was intravenously injected (5 mg/kg) immediately after induction of general anesthesia. Tumors were removed using a microsurgical technique with the YELLOW560 filter (Carl Zeiss Meditec, Oberkochen, Germany). In the most recent cases, biopsies at the tumor margins were performed to evaluate the ability of fluorescein to discriminate between fluorescent and nonfluorescent tissue at the lesion borders. RESULTS: Seventy-nine patients were included; most of them showed a bright, diffuse fluorescent staining that markedly enhanced tumor visibility; 11 melanomas presented a specific faint enhancement of the black pigmented central nodule with high fluorescence at tumor boundaries. Only in a minimal percentage of cases (N.=4-5.1%), fluorescein enhancement was tenuous, thus not providing a significant help during tumor resection. Altogether, in more than 90% of cases, SF was considered useful in the identification of tumoral tissue and in achieving a high rate of CM resection; thus, gross total resection was achieved in 96.2% (N.=76) of patients and in no case the detection of tumor remnants was an unexpected event. The resulted sensitivity and specificity of fluorescein in identifying tumor tissue at the tumor margin was 88.9% with a predictive positive value of 88.9%. No adverse event was registered during the postoperative course. 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 CM, suggesting a role in improving the extent of resection of these lesions.

Sporadic spinal psammomatous malignant melanotic nerve sheath tumor: A case report and literature review.

Background: Sporadic Spinal Psammomatous Malignant Melanotic Nerve Sheath Tumor (SSP-MMNST) is a rare subgroup of peripheral nerve sheath tumors arising along the spine. Only a few reports of SSP-MMNST have been described. In this paper, we review the literature on SSP-MMNST focusing on clinical, and diagnostic features, as well as investigating possible pathogenetic mechanisms to better implement therapeutic strategies. We also report an illustrative case of a young female presenting with cervicobrachial pain due to two SSP-MMNSTs arising from C5-6 right spinal roots. Case description: We report a case of a 28-year-old woman presenting with right arm weakness and dysesthesia. Clinical examination and neuroimaging were performed, and, following surgical removal of both lesions, a histological diagnosis of SSP-MMNST was obtained. Results: The literature review identified 21 eligible studies assessing 23 patients with SSP-MMNST, with a mean onset age of 41 years and a slight male gender preference. The lumbar district was the most involved spinal segment. Gross-total resection (GTR) was the treatment of choice in all amenable cases, followed in selected cases with residual tumor by adjuvant radiotherapy or chemotherapy. The metastatic and recurrence rates were 31.58% and 36.8%, respectively. Conclusion: Differently from common schwannomas, MMNST represents a rare disease with known recurrence and metastatization propensity. As reported in our review, SSP-MMNST has a greater recurrence rate when compared to other forms of spinal MMNST, raising questions about the greater aggressiveness of the former. We also found that residual disease is related to a higher risk of systemic disease spreading. This metastatic potential, usually associated with primary lumbar localization, is characterized by a slight male prevalence. Indeed, whenever GTR is unachievable, considering the higher recurrence rate, adjuvant radiation therapy should be taken into consideration.

Anesthesia-induced Takotsubo cardiomyopathy in trigeminal neuralgia: illustrative case.

BACKGROUND: Takotsubo syndrome (TS) represents a form of nonischemic cardiomyopathy characterized by sudden and temporary weakening of the myocardium. Many data suggest a primary role for sympathetic overstimulation in its pathogenesis. Nevertheless, these correlates are less easily identified during anesthesia. OBSERVATIONS: A 50-year-old female patient with a 4-year history of drug-resistant left trigeminal neuralgia. She was scheduled for surgical microvascular decompression. In the operating room, after induction of general anesthesia and oral intubation, the electrocardiogram revealed a significant ST segment elevation along with a sudden decrease in systolic blood pressure and heart rate. Administration of atropine caused a conversion into ventricular tachycardia. The advanced cardiac life support protocols were applied with prompt defibrillation and rapid recovery at sinus rhythm. A transthoracic echocardiogram revealed apical akinesia with ballooning of the left ventricle with a reduction of systolic function. An emergency coronary arteriography was performed, showing normal epicardial coronary vessels. After 4 days, echocardiography revealed normalization of the left ventricular function with improvement of the ejection fraction. LESSONS: In patients affected by trigeminal neuralgia, chronic pain can lead to a state of adrenergic hyperactivation, which can promote TS during the induction of general anesthesia, probably through the trigeminocardiac reflex.

Fluorescein sodium in the surgical treatment of pleomorphic xanthoastrocytomas: Results from a retrospective study.

Objective: Pleomorphic xanthoastrocytoma (PXA) is a rare brain tumor, most commonly affecting children and young adults. Surgical resection represents the mainstay of treatment, and extent of resection is associated with improved survival. In this study, we analyzed the role of sodium fluorescein (SF) in improving intraoperative visualization easing resection. Methods: Surgical database of FLUOCERTUM study (Besta Institute, Milan, Italy) was retrospectively reviewed to find pleomorphic xanthoastrocytomas and anaplastic xanthoastrocytomas, according to WHO-2016/2021 classification, surgically removed by a fluorescein-guided technique from March 2016 to February 2022. SF was intravenously injected (5mg/kg) immediately after induction of general anesthesia. Tumors were removed using a microsurgical technique with the YELLOW 560 filter (Carl Zeiss Meditec, Oberkochen, Germany). Results: Twelve patients (7 males and 5 females; 3 pediatric patients, mean age 10 years, range 5 to 13 years and 9 adult patients, mean age 50.6 years, range 35 to 63 years) underwent fluorescein-guided surgery. No side effects related to SF occurred. In all tumors, contrast enhancement on preoperative MRI correlated with intense, heterogeneous yellow fluorescence with bright fluorescent cystic fluid. Fluorescein was considered helpful in distinguishing tumors from viable tissue in all cases. Gross total resection was achieved in 8 cases (66.7%); in 4 cases, otherwise, the resection was subtotal with fluorescent residual spots to avoid neurological worsening (33.3%). Conclusions: The use of SF is a valuable method for safe fluorescence-guided tumor resection. Our data documented a positive effect of fluorescein-guided surgery on intraoperative visualization, suggesting a probable role in improving the extent of resection during yellow surgery of PXA.

Fluorescein-guided surgery for the resection of pilocytic astrocytomas: A multicentric retrospective study.

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.

Occipital Intradiploic Pseudomeningocele - A Rare Complication of Pediatric Posterior Cranial Fossa Surgery: Case Report and Review of the Literature.

INTRODUCTION: Intradiploic pseudomeningoceles, also called intradiploic cerebrospinal fluid (CSF) fistulas, are abnormal CSF collections between the two bony tables of the calvaria resulting from postsurgical CSF leakage. To date, only six cases of intradiploic pseudomeningocele have been reported, all occurring in the occipital area. In this paper, we report the seventh case of late-onset occipital intradiploic pseudomeningocele (OIP) occurring in a young female patient who underwent surgery for the removal of a cerebellar pilocytic astrocytoma. In this regard, we also review the literature on the few recognized cases of OIP. CASE PRESENTATION: The case of an 18-year-old female patient known to our institute for an operation 12 years earlier to remove a pilocytic astrocytoma is illustrated. At admission, the patient complained only of occasional orthostatic headache. Brain imaging demonstrated a pseudomeningocele extended intradiploically from the occipital squama to the condylar and clivus regions, thinning both occipital bone tables and dilating the CSF-filled diploe. Watertight duroplasty and cranioplasty were effectively performed. CONCLUSION: Pediatric patients undergoing posterior cranial fossa craniotomy/craniectomy may postoperatively develop OIP. In this setting, treatment of any dural CSF fistula should be considered because of the risk of progressive extension and bone erosion.

Diagnostic approach, therapeutic strategies, and surgical indications in intradural thoracic disc herniation associated with CSF leak, intracranial hypotension, and CNS superficial siderosis.

BACKGROUND AND PURPOSE: Intradural disc herniation (IDH) can manifest with radicular or medullary syndrome. In about 15% of cases, IDH may be responsible, through a dural laceration, for a CSF leak, determining spontaneous intracranial hypotension (SIH) and CNS superficial siderosis (CNSss). This paper attempts to present an overview on IDH as the cause for both CSF leak, and subsequent SIH, and CNSss, and to describe a peculiar clinical and neuroradiological scenario related to this condition. METHODS: A search on the PUBMED database was performed. Although the investigation did not rigorously follow the criteria for a systematic review (we consider only articles about thoracic IDH), nonetheless, the best quality evidence was pursued. Furthermore, an illustrative case was presented. RESULTS: A 69-year-old woman was referred to our hospital for slowly progressive gait disturbances and hearing impairment. Brain imaging revealed diffuse bilateral supratentorial and infratentorial superficial siderosis, mostly of the cerebellum, the eighth cranial nerves, and the brainstem. Spinal imaging disclosed a posterior disc herniation determining a dural tear at D6-D7. Lumbar puncture revealed low opening pressure and hemorrhagic CSF with siderophages. A posterior transdural herniectomy and dural sealing determined a stabilization of hearing and a significant improvement in both gait and balance. CONCLUSIONS: The diagnostic workup of CNSss with suspected CNS leak demands whole neuraxis imaging, especially in cases presenting SIH or myelopathic symptoms. This may avoid delays in detection of IDH and spinal dural leaks. The different forms of treatment available depend on the type and severity of the clinical picture.

Diagnostic and surgical management of primary central nervous system angioleiomyoma: A case report and literature review.

Angioleiomyoma (ALM) is a benign smooth muscle neoplasm that mainly occurs in lower extremities subcutaneous tissue and generally affects middle-aged adults. This tumor histotype may rarely localize intracranially, although only a few cases have been described in the literature. We report a case of intracranial ALM, whose differential diagnosis has been particularly challenging, and firstly provide a comprehensive radiological and intra-operative evaluation of a such rare entity. This represents also the first report of the use of intraoperative confocal microscopy in ALM and the first documented short-term recurrence. At this regard, a scoping literature review has been conducted with the aim of presenting the major clinical and diagnostic features along with the proposed therapeutic strategies.

Towards an Established Intraoperative Oncological Favorable Tool: Results of Fluorescein-Guided Resection from a Monocentric, Prospective Series of 93 Primary Glioblastoma Patients.

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.