Adam Shapira Levy

Caspase-1 is a central mediator of canonical inflammasome signaling and drives neuroinflammatory injury through interleukin-1β (IL-1β) and interleukin-18 (IL-18) maturation, gasdermin D (GSDMD)-mediated pyroptosis, and secondary inflammatory cascades. In spinal cord injury (SCI) and other neurologic disorders, experimental evidence links caspase-1 activation to blood–spinal cord barrier (BSCB) or blood–brain barrier (BBB) disruption, glial activation, neuronal and oligodendroglial injury, and worse functional outcomes. However, despite mechanistic rationale, the clinical role of caspase-1 as a biofluid biomarker remains incompletely defined. This review summarizes preclinical and clinical evidence regarding caspase-1 and inflammasome-associated proteins across cerebrospinal fluid (CSF), serum, plasma, and other biofluids, emphasizing SCI and translational neuroinflammation. Human studies suggest that inflammasome-associated markers may reflect acute inflammatory activity and injury severity, but direct caspase-1 measurement is limited by small cohorts, heterogeneous sampling windows, variable assay platforms, and inconsistent correlations with neurologic outcomes. Overall, caspase-1 remains a biologically plausible but not clinically established biomarker. Future studies should incorporate longitudinal sampling, standardized assays, paired measurement of IL-1β, IL-18, GSDMD, and other pyroptosis-related markers, and integration with imaging and functional outcomes. Such work may clarify whether caspase-1 can serve as a clinically actionable biomarker, prognostic indicator, or therapeutic monitoring target in SCI and related neuroinflammatory conditions.

The Mitogen-activated protein kinase kinase (MEK) protein family has dual-specificity protein kinases with a myriad of cellular functions that include but are not limited to cell survival, cell division, immunologic response, angiogenesis, and cellular senescence. MEK is crucial in the MAPK signaling pathway, regulating different organ systems, including the CNS. Increased activation and dysregulation of the MEK pathway is reportedly observed in 30% of all malignancies. The diversity of MEK renders it a prime target for inhibition in treating cancer. MEK inhibition has been studied in the context of melanoma, non-small cell lung cancer, breast cancer, and colorectal cancer, among others. The standard treatment for glioblastoma (resection, temozolomide, and radiation) remains relatively futile, which warrants alternative treatment options. Therefore, MEK inhibition has garnered more attention in recent years as investigators have explored its role in treating the most aggressive and most common primary brain tumor, glioblastoma. MEK inhibitors have shown efficacy in pre-clinical investigations as well as some promise in clinical trials which have demonstrated improved overall and progression-free survival. This underscores the potential of MEK inhibition in glioblastoma therapy and represents an area that likely warrants further research. However, there are few comprehensive and unifying reviews discussing the current state of MEK inhibition in glioblastoma therapy. We begin this review by detailing the normal function of MEK as it pertains to the CNS. We then compiled relevant pre-clinical and clinical studies to investigate recent research discussing the role of MEK inhibition in glioblastoma therapy.

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.

Introduction: Penetrating spinal cord injuries present unique clinical scenarios with high variability in presentation and management. These injuries are rare, accounting for 0.8% of annual penetrating spine injuries in the United States, with knives being the most common penetrating object. Retention of the knife blade further complicates management, with greater risk of infection and progressive neurologic injury. Given the rarity and variability of such injuries, preferred management for penetrating-knife spinal cord injuries (PKSCI), especially those with retained knife blades, remains contested. Furthermore, the management of PKSCI with concurrent lung injury is poorly described within the literature. Case Report: Here we discuss a unique case of a neurologically intact adult male who suffered a large lower thoracic PKSCI with complete dural transection and lung involvement. The patient arrived with the blade in situ while maintaining full neurologic function. Emergent imaging revealed the blade trajectory passing through the T8 lamina exiting the spinal canal at the costovertebral junction with involvement of the lung parenchyma and associated pneumorrhachis and pneumothorax. The patient was brought to the operating room where the blade was removed under direct visualization, the dura was repaired, and pneumothorax was stabilized. Conclusion: We describe in this case the choice of imaging, method of blade removal, cerebrospinal fluid leak management, dural repair, and concurrent lung injury management that afforded a favorable, ASIA class E outcome with complete preservation of neurologic function.

OBJECTIVE: Resection of spinal nerve sheath tumors (SNSTs) typically necessitates laminectomy, often with facetectomy, for adequate exposure of tumor. While removal of bone affords a greater operative window and extent of resection, it places the patient at greater risk for spinal instability. Although studies have identified risk factors for fusion at the time of tumor resection, there has yet to be a study assessing long-term stability following SNST resection. In this study, the authors sought to identify preoperative and operative risk factors that predispose to long-term spinal instability and investigate clinical variables associated with greater risk for subsequent fusion in the time following initial SNST resection. METHODS: An institutional registry of spinal surgeries was queried at a single institution over a 20-year period. Demographic, clinical, and operative variables were recorded retrospectively and investigated for predictive value of several postoperative sequelae. RESULTS: A total of 122 SNST cases among 112 patients were included. At a mean follow-up time of 27.7 months, patients with a history of neurofibromatosis type 2 (NF2) (p = 0.014) and those who had undergone a laminectomy of ≥ 4 levels at the time of initial SNST resection (p = 0.028) were more likely to present with some degree of structural abnormality or neurological deficit following their initial surgery. The presence of facetectomy, degree of laminectomy, and level of spinal surgery were not found to be predictors of future instability. Ultimately, there was no significant predictor for true spinal instability following index surgery without fusion. A secondary analysis showed that an entirely extradural location (p = 0.044) and facetectomy at index surgery (p = 0.012) were predictive of fusion being performed at the time of tumor resection. Four of the 112 patients required fusion after their index SNST resection, 3 of whom underwent fusion for instability at the level of the index surgery. No variables were identified as predictive for future instrumentation. CONCLUSIONS: Ultimately, the authors conclude that resection of SNSTs does not always necessitate fusion, and good outcomes can be obtained with motion-preserving techniques and minimizing facetectomy when possible. Patients with a history of NF2 and those with SNSTs that required ≥ 4-level laminectomy were more likely to exhibit some degree of structural abnormality and/or neurological deficit localized to the index level defined as either new or worsening spinal instability and/or new or worsening neurological deficit at last follow-up; however, no variable was found to be predictive of true spinal instability. Furthermore, a complete facetectomy at initial SNST resection and entirely extradural tumor location were noted to be associated with fusion at index surgery. Lastly, the authors were unable to identify a clinical predictor for future instrumentation.

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 cm ³ ) 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.