Intrathecal chemotherapy for leptomeningeal disease in high-grade gliomas: a systematic review.

BACKGROUND: Leptomeningeal disease (LMD) secondary to high grade glioma (HGG), such as glioblastoma (GBM), are characterized by the spread of tumor cells to the leptomeninges which further complicates treatment approaches. Intrathecal (IT) chemotherapy has surfaced as a potential strategy to bypass the blood-brain barrier and address the challenges posed by disseminated disease. Here, we present a review of the safety and efficacy of IT chemotherapy in the treatment of LMD secondary to HGG. METHODS: A systematic review following PRISMA guidelines was conducted searching PubMed and Embase from January 1995 to September 2022 using specified terms related to IT chemotherapy for LMD. Included articles involved patients diagnosed with LMD from HGG, treated with intrathecal chemotherapy, and provided survival data. Data, including demographics, tumor characteristics, treatment, and survival information, were collected and independently extracted. RESULTS: A total of 68 patients across 10 clinical studies were diagnosed with LMD from HGG and included in the review. Among these patients, the average age at diagnosis was 44.2 years. GBM was the most common tumor type (n = 58, 85.3%). A majority of the patients presented with recurrent disease (n = 29, 60.4%). The review encompassed various IT chemotherapy regimens, including mafosfamide, thio-TEPA, 5-fluoro-2'-deoxyuridine (FdUrd), methotrexate (MTX), and cytarabine; however, dosages and frequencies were inconsistently reported. The mean progression-free survival (PFS) and overall survival (OS) for this cohort were 7.5 months and 11.7 months, respectively. Common side effects of IT chemotherapy included headaches, nausea, and vomiting, with more severe complications such as myelotoxicity, disseminated intravascular coagulopathy, meningitis, and gastrointestinal toxicity reported in some cases. CONCLUSION: LMD continues to be an uncommon complication associated with HGG with a poor prognosis. This article provides an overview of the presently available literature on IT chemotherapy for LMD secondary to HGG, and their respective treatment protocols with overall survival attributes. Additional research is warranted to ascertain how to maximize the potential efficacy of IT chemotherapy as a treatment option.

Influence of instrumentation type on outcomes after surgical management of spondylodiscitis: a systematic review and meta-analysis.

OBJECTIVE: Spondylodiscitis refers to infection of the intervertebral disk and neighboring structures. Outcomes based on instrumentation type are not well reported in the literature, but are important in establishing guidelines for surgical management of spondylodiscitis. This study aims to clarify the effect of instrumentation material selection on clinical and radiographic outcomes in patients with spondylodiscitis. METHODS: Studies that evaluated the use of polyetheretherketone (PEEK), titanium, allograft, and/or autologous bone grafts for spondylodiscitis were identified in the literature. Radiographic and clinical data were analyzed using a meta-analysis of proportions, with estimated risk and confidence intervals reported for our primary study outcomes. RESULTS: Thirty-two retrospective studies totaling 1088 patients undergoing surgical management of spondylodiscitis with PEEK, TTN, allograft, and autologous bone graft instrumentation were included. There were no differences in fusion rates (p-interaction = 0.55) with rates of fusion of 93.4% with TTN, 98.6% with allograft, 84.2% with autologous bone graft, and 93.9% with PEEK. There were no differences in screw loosening (p-interaction = 0.52) with rates of 0.33% with TTN, 0% with allograft, 1.3% with autologous bone graft, and 8.2% with PEEK. There were no differences in reoperation (p-interaction = 0.59) with rates of 2.64% with TTN, 0% with allograft, 1.69% with autologous bone graft, and 3.3% with PEEK. CONCLUSIONS: This meta-analysis demonstrates that the choice of instrumentation type in the surgical management of spondylodiscitis resulted in no significant differences in rate of radiographic fusion, screw loosening, or reoperation. Future comparative studies to optimize guidelines for the management of spondylodiscitis are needed.

Structure-sparing resection for the management of cervical chordomas: a retrospective institutional series.

OBJECTIVE: Chordomas are a rare and relatively slow-growing malignancy of notochordal origin with a nearly 50% recurrence rate. Chordomas of the cervical spine are particularly challenging tumors given surrounding vital anatomical structures. Although standard in other areas of the spine, en bloc resection of cervical chordomas is exceedingly difficult and carries the risk of significant postoperative morbidity. Here, the authors present their institutional experience with 13 patients treated with a structure-sparing radical resection and adjuvant radiation for cervical chordomas. METHODS: Records of the standing senior author and institutional database of spinal surgeries were retrospectively reviewed for surgically managed cervical and high thoracic chordomas between 1997 and 2022. Chordomas whose epicenter was cervical but touched the clivus or had extension to the thoracic spine were included in this series. Clinical and operative data were gathered and analyzed for the index surgery and any revisions needed. Outcome metrics such as recurrence rates, complication rates, functional status, progression-free interval (PFI) and overall survival (OS) were evaluated. RESULTS: The median patient age at diagnosis was 57 (range 32-80) years. The median modified Rankin Scale (mRS) score at the time of presentation was 1 (range 0-4). Approximately 40% of tumors were located in the upper cervical spine (occiput-C2). The median time from diagnosis to surgery was 74.5 (range 10-483) days. Gross-total resection was achieved in just under 40% of patients. All patients received adjuvant radiotherapy. The mean duration of follow-up was 4.09 years, with a mean PFI of 3.80 (range 1.16-13.1) years. Five patients experienced recurrence (38.5%). The mean OS was 3.44 years. Three patients died during the follow-up period; 2 due to disease progression and 1 died in the immediate postoperative period. One patient was lost to follow-up. A significant positive relationship was identified between high cervical tumor location and disease recurrence (p = 0.021). CONCLUSIONS: While en bloc resection is appropriate and feasible for tumors in the sacral spine, the cervical region poses a significant technical challenge and is associated with increased postoperative morbidity. Radical resection may allow for achievement of negative operative margins and, along with sparing postoperative morbidity following resection of cervical chordomas, maintaining a similar rate of recurrence when compared with en bloc resection while preserving quality of life.

Surgical management of brain metastasis from ovarian cancer: a systematic review and case series.

OBJECTIVE: Ovarian cancer is a rare origin of brain metastasis (BM), with an incidence of only 1%-3%. Consequently, the literature is sparse, and no treatment consensus guideline is available for ovarian BM. The authors conducted a systematic review of ovarian BM and performed a combined pooled cohort survival analysis with their case series. METHODS: A systematic review of PubMed, Scopus, and Web of Science consistent with PRISMA guidelines along with an institutional retrospective chart review was conducted. Inclusion criteria for the systematic review included patients with confirmed BM and primary ovarian cancer, reported perioperative complications and outcomes, differentiated histology, and explicitly reported individual patient data. Reviews, commentaries, technical notes, and articles without English-language translations were excluded. The Newcastle-Ottawa Quality Assessment Scale was used independently by the first and second authors to assess the quality of each article. The authors performed univariate and multivariate analyses of several survival prognostic factors. Kaplan-Meier curves were generated for significant prognostic factors in the univariate analysis. RESULTS: A total of 48 patients with individual data across 34 studies and 8 patients from the authors' institution were included. All patients (n = 56) underwent resection for BM; 83.9% received adjuvant radiotherapy following surgery and 41.1% of patients received adjuvant chemotherapy. The median progression-free survival was 12 months (range 2-43 months). The median overall survival was 9 months (range 1-49 months). On univariate analysis, a single BM and no extracranial metastasis conferred a survival benefit, while clear cell carcinoma as the primary histology corresponded to worsened OS. Multivariable analysis showed that age > 50 years (p = 0.002) and > 1 BM (p < 0.001) were risk factors for poor prognosis. Protective factors included the addition of the following multimodal adjuvant therapy with surgery: radiotherapy (p = 0.002), chemotherapy and radiotherapy (p = 0.005), and stereotactic radiosurgery (p = 0.002). CONCLUSIONS: Although the scarcity of published individual patient data hinders the determination of optimal management, the authors' analysis highlights that multimodal therapies, a single cranial lesion, and age < 50 years are associated with increased survival for patients with ovarian BMs.

Same-day discharge after craniotomy for brain tumor resection: enhancing patient selection through a prognostic scoring system.

OBJECTIVE: Neurosurgery, among other surgical fields, is amid a shift in patient management with enhanced recovery and same-day discharge (SDD) protocols slowly becoming more popular and feasible. While such protocols reduce the risk of nosocomial complications and improve patient satisfaction, appropriate patient selection remains an area of debate. The authors aimed to better quantify selection criteria through a prospective follow-up study of patients undergoing brain tumor resection with SDD. METHODS: Three arms of analysis were carried out. First, clinical data of SDD patients were prospectively collected between August 2021 and August 2022. In parallel, a retrospective analysis of patients who qualified for SDD but were excluded at surgeon clinical discretion over the same period was performed. Third, a comparative analysis of the pilot and follow-up studies was done from which a clinical scoring system for patient selection was derived. RESULTS: Over the duration of the study, 31 of 334 patients were selected for SDD while 59 qualified for SDD by previously defined criteria but were not selected at the surgeon's discretion. There was no difference in outcomes between the two groups, and there were no postoperative complications among the SDD group within 30 days of surgery. Preoperative clinical characteristics found to be significantly different between the two cohorts (left-sided lesion, extra-axial pathology, prior treatment of brain tumor, and tumor volume ≤ 11.75 cm3) were included in a predictive scoring system for successful SDD. The scoring system was found to significantly predict high or low likelihood for successful SDD when tested on the mixed prospective cohort. CONCLUSIONS: This study provides a straightforward clinical scoring system for appropriate selection of candidates for SDD after craniotomy for brain tumor resection. This clinical tool aims to aid clinicians in appropriate admission course selection and builds on the growing literature surrounding same-day and outpatient cranial neurosurgery.

Assessing Survival, Distribution, and Optimal Loading Technique of Schwann Cell-Derived Exosomes Into Second-generation Axon Guidance Channels.

INTRODUCTION: Peripheral nerve injury (PNI) occurs in approximately 3% of all trauma patients and can be challenging to treat, particularly when injury is severe such as with a long-segmental gap. Although peripheral nerves can regenerate after injury, functional recovery is often insufficient, leading to deficits in the quality of life of patients with PNI. Although nerve autografts are the gold standard of care, there are several disadvantages to their use, namely a lack of autologous nerve material for repair. This has led to the pursuit of alternative treatment methods such as axon guidance channels (AGCs). Second-generation AGCs have been shown to be able to deliver growth-enhancing substrates for nerve repair directly to the injury site. Although our laboratory has had success with second-generation AGCs filled with Schwann cells (SCs), SCs have their own set of issues clinically. Because of this, we have begun to utilize SC-derived exosomes as an alternative, as they have the appropriate protein markers, associate to axons in high concentrations, and are able to improve nerve regeneration. However, it is unknown how SC-derived exosomes may react within second-generation AGCs; thus, the aim of the present study was to assess the ability of SC-derived exosomes to be loaded into a second-generation AGC and how they would distribute within it. MATERIALS AND METHODS: A total of 4 dry second-generation AGCs were loaded with SC-derived exosomes that were derived from green fluorescent protein (GFP)-labeled SCs. They were subsequently frozen and sliced before imaging. RESULTS: Here, we present findings that SC-derived exosomes can be loaded into second-generation AGCs through our established loading method utilizing negative pressure and are able to survive and equally distribute along the length of the AGC. CONCLUSIONS: Although only 4 second-generation AGCs were utilized, these findings indicate a potential use for SC-derived exosomes within second-generation AGCs to treat severe PNI. Future research should focus on exploring this in greater detail and in different contexts to assess the ability of SC-derived exosomes to survive at the site of injury and treat PNI.

Optimizing outpatient neurosurgery: evaluating ambulatory surgery and same-day discharge following intracranial tumor surgery and endoscopic third ventriculostomy.

OBJECTIVE: Outpatient surgery and same-day discharge are developing fields that align with the evolving needs of modern healthcare, presenting a notable advantage by reducing patient susceptibility to nosocomial infections, thromboembolic complications, and medical errors. When paired with enhanced recovery after surgery protocols, they hold promise in safely transitioning certain patients undergoing cranial surgery to outpatient care. This study aimed to evaluate discharge on the same day of surgery after intracranial tumor resection and endoscopic third ventriculostomy (ETV) and to investigate potential associations with anesthesia methods, complications, and readmission rates. METHODS: A retrospective analysis of patients scheduled for planned discharge on the same day of surgery between August 2020 and October 2023 was conducted. Data included patient demographic characteristics, preoperative clinical deficits, diagnosis, findings on preoperative and postoperative MRI, lesion characteristics, complications, and readmission rates. RESULTS: A total of 202 patients were included in the study. The mean age was 56.8 years and 117 (57.9%) patients were female. Patients were admitted the evening before surgery to obtain preoperative clearance and undergo MRI. The most common diagnoses were metastasis (23.3%), meningioma (20.8%), glioblastoma (12.4%), and low-grade glioma (10.4%). Craniotomy (46.5%), stereotactic needle biopsy (35.1), and ETV (6.9%) were the most common procedures performed. Thirteen (6.4%) patients underwent awake craniotomy, and 189 (93.6%) surgical procedures were conducted under general anesthesia. Complications occurred in 1.5% of patients, with no permanent complications observed during a mean follow-up of 9.3 months. In total, 179 (88.6%) patients were successfully discharged on the same day of surgery. The median length of hospitalization was 26.8 hours, with the median length of postoperative stay being 7 hours. Twenty-three (11.4%) patients were deemed ineligible for discharge on postoperative day 0 and instead discharged on postoperative day 1. The reasons for these delays included further clinical monitoring (n = 12), social factors (n = 4), and patient preference (n = 7). Age was positively correlated with length of hospitalization (p = 0.006). In total, 6.4% of patients were readmitted within 1-30 days after discharge, with 2.5% readmitted to the department of neurosurgery. CONCLUSIONS: This study demonstrates the safety and feasibility of discharge on the same day of surgery, with a high success rate and low complication rates. Early discharge did not increase morbidity or readmission rates. Implementation of clear discharge protocols and thorough patient education are crucial for successful same-day discharge programs in neurosurgery.

Recurrent Peroneal Intraneural Ganglion Cyst: Management and Review of the Literature.

Intraneural ganglion cysts have been reported to affect the common peroneal nerve. Peroneal intraneural ganglion cysts are managed through surgical intervention. Despite surgical intervention, intraneural ganglion cysts can recur. Common intraneural ganglion cyst recurrence patterns have been proposed based on the initial surgical management of the cyst. These patterns all emphasize the importance of treatment of the proximal tibiofibular (TF) joint to reduce the risk of cyst recurrence. Although joint resection is the favored intervention in the literature, joint arthrodesis is an option for certain patients. Here, we present a case of a peroneal intraneural ganglion cyst and its recurrence in a 36-year-old male who had previously undergone surgical removal of the cyst three months prior, as well as a review of the current literature that aims to add to our current understanding of intraneural cysts.

Contralateral transfalcine approach for resection of right medial frontal AVM.

Brain arteriovenous malformations (AVMs) are high flow vascular lesions that can cause significant morbidity and mortality [1-6]. We present a case of a 23-year-old woman who initially presented to an outside institution with a ruptured right medial frontal Spetzler Martin grade II AVM. An EVD was placed and a diagnostic angiogram with partial embolization was performed. She was then transferred to our institution two months post rupture for further care. On arrival, she was trached with eyes opening to voice and localizing in bilateral upper extremities and withdrawing in bilateral lower extremities. Diagnostic angiogram demonstrated arterial supply from the right pericallosal and callosomarginal artery, right posterior cerebral artery callosomarginal branch, distal left anterior cerebral artery (ACA) branches with venous drainage via a cortical vein to the superior sagittal sinus. The patient underwent preoperative embolization of the ACA feeders followed by a contralateral interhemispheric transfalcine approach. An interhemispheric dissection was performed down to the corpus callosum and AVM feeders and draining veins were identified. The falx was then incised to expose the right medial frontal lobe. The AVM was circumferentially dissected and resected. Postoperative imaging demonstrated complete resection of the AVM. She remained at her neurological baseline immediately postoperatively and was discharged to inpatient rehab. The patient made a remarkable recovery and at three months follow up, she no longer required a tracheostomy and was neurologically intact with no complaints except for mild memory difficulties. In this video, we demonstrate the step-by-step surgical technique and review the benefits of the contralateral transfalcine approach for resection of a ruptured right medial frontal Spetzler Martin grade II AVM. The patient consented to the procedure and to the publication of her imaging in this surgical video.

Clinical applications of electrical stimulation for peripheral nerve injury: a systematic review.

Introduction: Peripheral nerve injuries are common neurologic injuries that are challenging to treat with current therapies. Electrical stimulation has been shown to accelerate reinnervation and enhance functional recovery. This study aims to review the literature on clinical application of electrical stimulation for peripheral nerve injury. Methods: PubMed and Embase were sourced from 1995 to August 2022. Selection was based on predetermined inclusion/exclusion criteria. Eight hundred and thirty-five articles were screened with seven being included in this review. Results: Two hundred and twenty-nine patients with peripheral nerve injuries were represented. Six of the studies were randomized controlled trials. A variety of nerve injuries were represented with all being in the upper extremity and supraclavicular region. Electrical stimulation protocols and evaluation varied. Electrodes were implanted in four studies with one also implanting the stimulator. Length of stimulation per session was either 20 mins or 1 h. Median stimulation frequency was 20 Hz. Stimulation intensity varied from 3 to 30V; pulse width ranged from 0.1 to 1.007 ms. Three protocols were conducted immediately after surgery. Patients were followed for an average of 13.5 months and were evaluated using electrophysiology and combinations of motor, sensory, and functional criteria. Discussion: Patients who received electrical stimulation consistently demonstrated better recovery compared to their respective controls. Electrical stimulation for peripheral nerve injury is a novel treatment that has not been well-studied in humans. Our review illustrates the potential benefit in implementing this approach into everyday practice. Future research should aim to optimize protocol for clinical use.

Resection of a lumbar intradural tumor.

Background: Myxopapillary ependymomas and schwannomas represent the most common tumors of the conus medullaris and cauda equina. Here, we present the surgical resection of a 64-year-old male with a lumbar intradural tumor. Case Description: A 64-year-old male presented with several months of the lower extremity weakness, pain, and bowel/bladder dysfunction. Magnetic resonance imaging demonstrated a large L3-5 intradural lesion, and surgical resection using intraoperative neuromonitoring with somatosensory evoked potentials (SSEPs), motor evoked potentials (MEPs), free-running electromygraphy (EMGs), and direct sphincter monitoring was recommended. After an L2-S1 laminectomy was performed, intraoperative ultrasound was used to confirm the cranial and caudal extent of the tumor. The dural was opened using a midline approach, and the tumor was quickly visualized. Through careful dissection, the tumor was debulked and gross total resection was ultimately achieved through a piecemeal resection. Hemostasis was frequently required throughout the case, as the tumor was highly vascular. Postoperatively, the patient was at his neurologic baseline and was discharged to rehab on postoperative day 4. The final pathology revealed the intradural lesion was a paraganglioma. Conclusion: Early intervention and gross total resection of spinal intradural tumors are associated with optimal patient outcomes. Additional adjuncts, such as ultrasound, are beneficial and can help achieve gross total tumor resection.

Surgical Management of a Spinal Dural Arteriovenous Fistula.

Spinal dural arteriovenous fistulas (SDAVFs) may have subtle clinical presentations and are often misdiagnosed. Clinical status gradually deteriorates following symptom onset making prompt identification and management essential. Here we present a case of a 67-year-old patient with rapidly progressing motor and sensory deficits to eventual right hemiplegia. Following imaging and surgical intervention, a thoracic SDAVF was identified and resected. This case report highlights a unique SDAVF with a stroke-like presentation. For patients with such presentation, without a clear source of intracranial pathology, spinal causes such as SDAVF could be considered.