Significant tumor compression of the middle cerebellar peduncle is associated with worse facial nerve outcomes and lower extent of resection in surgery for medium-sized vestibular schwannomas - A radiographic analysis of a case series.

BACKGROUND AND OBJECTIVE: Optimizing the extent of resection (EOR) and facial nerve outcomes (FNO) remain a challenge in medium to large vestibular schwannomas (VS). Currently, tumor size has been the only consistently reported factor predicting FNO and EOR. Here, we sought to evaluate whether the degree of the tumor's compression on the middle cerebellar peduncle (PC) influences FNO and EOR in medium to large VS. METHODS: This retrospective case series included 99 patients who underwent surgical resection of their VSs from 2014 to 2022. Preoperative MR imaging was used to measure the degree of PC. Patient medical records were queried to determine the EOR and FNO. RESULTS: Patients with unfavorable FNO (HB 3 +) immediately post-op had significantly greater PC than those with favorable FNO (19.9 vs. 15.4 mm, P = .047). This significance was not observed at the last follow-up but there was a trend. When medium-sized tumors (15-30 mm) were analyzed separately, patients with unfavorable FNO immediate post-op and at last follow-up had significantly greater PC than their favorable counterparts (14.1 vs 8.7 mm). Significantly greater PC was also observed in patients who underwent subtotal resection (20.7 mm) compared to near (14.3 mm) and gross total resection (10.8 mm). Multivariate analyses confirmed these findings in medium-sized tumors, but not large-sized tumors. CONCLUSION: The degree of PC as measured on preoperative imaging can predict FNO and EOR in medium-sized vestibular schwannomas. Medium-sized tumors with > 15 mm of PC likely will have worse FNO and lower EOR.

Immuno-Transcriptomic Profiling of Blood and Tumor Tissue Identifies Gene Signatures Associated with Immunotherapy Response in Metastatic Bladder Cancer.

Blood-based biomarkers represent ideal candidates for the development of non-invasive immuno-oncology-based assays. However, to date, no blood biomarker has been validated to predict clinical responses to immunotherapy. In this study, we used next-generation sequencing (RNAseq) on bulk RNA extracted from whole blood and tumor samples in a pre-clinical MIBC mouse model. We aimed to identify biomarkers associated with immunotherapy response and assess the potential application of simple non-invasive blood biomarkers as a therapeutic decision-making assay compared to tissue-based biomarkers. We established that circulating immune cells and the tumor microenvironment (TME) display highly organ-specific transcriptional responses to ICIs. Interestingly, in both, a common lymphocytic activation signature can be identified associated with the efficient response to immunotherapy, including a blood-specific CD8+ T cell activation/proliferation signature which predicts the immunotherapy response.

Intraoperative View of a Multinodal, Paralysis-Inducing Spinal Melanocytoma: Case Report and Literature Review.

Melanocytomas arising from the leptomeningeal melanocytes within the central nervous system are a rare occurrence, accounting for 0.06%-0.1% of brain tumors and having an incidence of 1/10 million people per year.1-14 Here, we describe the case of 68-year-old male presenting with bilateral lower extremity weakness progressing to paralysis and urinary incontinence (Video 1). Upon examination, this gentleman had no sensation below T11. Magnetic resonance imaging showed multiple contrast-enhancing lesions with a major intradural lesion at level T11 arising from the ventrolateral surface and causing severe spinal cord compression. The multifocal nature of this tumor further adds to its rarity. Interdisciplinary indication for surgical resection of the intradural lesion was made. This was accomplished through a T11 laminectomy and concomitant T11-12 stabilization with neuromonitoring. Pathologic analysis of the resected tumor identified an S100+, HMB45+, pigmented melanocytoma. No complications occurred during the procedure. The patient was discharged to rehabilitation with persistent neurologic deficits. Routine follow-up is indicated given the high rates of recurrence and the multiple remaining tumor nodules.14.

The local microenvironment drives activation of neutrophils in human brain tumors.

Neutrophils are abundant immune cells in the circulation and frequently infiltrate tumors in substantial numbers. However, their precise functions in different cancer types remain incompletely understood, including in the brain microenvironment. We therefore investigated neutrophils in tumor tissue of glioma and brain metastasis patients, with matched peripheral blood, and herein describe the first in-depth analysis of neutrophil phenotypes and functions in these tissues. Orthogonal profiling strategies in humans and mice revealed that brain tumor-associated neutrophils (TANs) differ significantly from blood neutrophils and have a prolonged lifespan and immune-suppressive and pro-angiogenic capacity. TANs exhibit a distinct inflammatory signature, driven by a combination of soluble inflammatory mediators including tumor necrosis factor alpha (TNF-ɑ) and Ceruloplasmin, which is more pronounced in TANs from brain metastasis versus glioma. Myeloid cells, including tumor-associated macrophages, emerge at the core of this network of pro-inflammatory mediators, supporting the concept of a critical myeloid niche regulating overall immune suppression in human brain tumors.

IL-6 in spinal cord injury: could immunomodulation replace immunosuppression in the management of acute traumatic spinal cord injuries?

Traumatic spinal cord injuries (SCI) result in devastating impairment to an individual's functional ability. The pathophysiology of SCI is related to primary injury but further propagated by secondary reactions to injury, such as inflammation and oxidation. The inflammatory and oxidative cascades ultimately cause demyelination and Wallerian degeneration. Currently, no treatments are available to treat primary or secondary injury in SCI, but some studies have shown promising results by lessening secondary mechanisms of injury. Interleukins (ILs) have been described as key players in the inflammation cascade after neuronal injury; however, their role and possible inhibition in the context of acute traumatic SCIs have not been widely studied. Here, we review the relationship between SCI and IL-6 concentrations in the CSF and serum of individuals after traumatic SCIs. Furthermore, we explore the dual IL-6 signaling pathways and their relevance for future IL-6 targeted therapies in SCI.

Vein of Galen Malformations in adults.

OBJECTIVE: Vein of Galen Malformations (VoGM) are rare vascular malformations, typically seen in pediatric age groups. Even more rarely, VoGM's may be seen later in adulthood. In this case report and systematic review, we provide a thorough description of the current literature as well as provide a case example exploring the diagnosis, imaging, treatment, and management of VoGM in adults. METHODS: In accordance with PRISMA guidelines, we performed a systematic literature search for all relevant cases and case series of VoGM in adult patients. The reference list of all articles were reviewed for additional relevant cases. Articles were included if they described a VoGM of a patient over the age of 18 years old and published in English. 149 articles were originally identified and 26 described cases met our inclusion criteria. RESULTS: In our literature review we found 26 patients that met our inclusion criteria. We found 14 male patients and 12 female patients. The mean age at presentation was 37.2 years (median=34 years, SD= 13.6 years). The most common presenting symptoms of patient were headache (n = 9), seizure (n = 6), and vomiting (n = 4). Of the 12 cases which clearly reported the subtype of VoGM, the choroidal type was more frequently seen (n = 10) compared to the mural type (n = 2). In 3 patients, the VoGM was thrombosed at time of diagnosis. Of the 26 patients, endovascular treatment was performed most frequently (n = 8) but some received microsurgical treatment (n = 4) or were treated conservatively (n = 6). Other treatment modalities included (ventriculoperitoneal shunt, ventriculostomy) (n = 5). In 3 cases treatment was not specified. In comparison to VoGM seen in pediatric or neonatal populations, VoGM in adults generally resulted in more favorable outcomes with only 2 patients reported to have passed away following treatment. CONCLUSION: VoGM remains a rare finding amongst the adult population. Hence, we described the clinical presentation, treatment modalities, and outcomes of the cases described in the English literature. Perhaps due to the rate of thrombosis and the unique angioarchitecture seen in adult VoGM patients, outcomes were generally more favorable than those described in the literature in pediatric or neonate VoGM patients.

Cranial imaging window implantation technique for longitudinal multimodal imaging of the brain environment in live mice.

Intravital two-photon microscopy of the mouse brain requires visual access without affecting normal cognitive functions, which is crucial for longitudinal imaging studies that may last several months. In this protocol, we describe the surgical implantation of a metal-free cranial imaging window, which can be used to perform two-photon microscopy and magnetic resonance imaging in the same animal. This multimodal imaging platform enables the investigation of dynamic processes in the central nervous system at a cellular and macroscopic level. For complete details on the use and execution of this protocol in the context of brain cancer, please refer to Zomer et al.1.

Using Frailty Measures to Predict Functional Outcomes and Mortality After Type II Odontoid Fracture in Elderly Patients: A Retrospective Cohort Study.

STUDY DESIGN: Single-center retrospective cohort study. OBJECTIVES: Type II odontoid fractures occur disproportionately among elderly populations and cause significant morbidity and mortality. It is a matter of debate whether these injuries are best managed surgically or conservatively. Our goal was to identify how treatment modalities and patient characteristics correlated with functional outcome and mortality. METHODS: We identified adult patients (>60 years) with traumatic type II odontoid fractures. We used multivariate regression controlling for patient demographics, Glasgow Coma Scale (GCS) score, Charlson Comorbidity Index (CCI), modified Rankin Scale (mRS) score, modified Frailty Index (mFI-5 and mFI-11), fracture displacement, and conservative vs operative treatment. RESULTS: Of the 59 patients (mean age 77.9 years), 24 underwent surgical intervention and 35 underwent conservative management. Operatively managed patients were younger (73.4 vs 80.6 years, P < .001) and had higher degree of fracture displacement (3.5 vs 1.0 mm, P = .002) than conservatively managed patients but no other differences in baseline characteristics. Twenty-four patients (40.7%) died within the study period (median time to death: 376 days). There were no differences between treatment groups in functional outcomes (mRS or Frankel Grade) or mortality (33.3% in operative group vs 45.7%, P = .34). There was a statistically significant correlation between higher presentation mRS score and subsequent mortality on multivariate analysis (OR = 2.06, 95% CI 1.04-4.10, P = .039), whereas surgical intervention, age, GCS score, CCI, mFI-5, mFI-11, sex, and fracture displacement were not significantly correlated. CONCLUSIONS: Mortality after type II odontoid fractures in elderly patients is common. mRS score at presentation may help predict mortality more accurately than other patient factors.

Cerebral Aneurysm and Interleukin-6: a Key Player in Aneurysm Generation and Rupture or Just One of the Multiple Factors?

Intracranial aneurysm (IA) rupture is a common cause of subarachnoid hemorrhage (SAH) with high mortality and morbidity. Inflammatory interleukins (IL), such as IL-6, play an important role in the occurrence and rupture of IA causing SAH. With this review we aim to elucidate the specific role of IL-6 in aneurysm formation and rupture in preclinical and clinical studies. IL-6 is a novel cytokine in that it has pro-inflammatory and anti-inflammatory signaling pathways. In preclinical and clinical studies of IA formation, elevated and reduced levels of IL-6 are reported. Poor post-rupture prognosis and increased rupture risk, however, are associated with higher levels of IL-6. By better understanding the relationships between IL-6 and IA formation and rupture, IL-6 may serve as a biomarker in high-risk populations. Furthermore, by better understanding the IL-6 signaling mechanisms in IA formation and rupture, IL-6 may optimize surveillance and treatment strategies. This review examines the association between IL-6 and IA, while also suggesting future research directions.

Getting the guts to expand stroke treatment: The potential for microbiome targeted therapies.

AIMS: This review focuses on the recent literature regarding the role of the gut-brain axis (GBA) following ischemic stroke. DISCUSSION: Stroke is the 5th leading cause of death and disability in the United States; however, few therapies have been developed to improve prognoses. There is a plethora of evidence suggesting peripheral inflammatory responses play a large role in the pathogenesis of stroke. Additionally, hyperglycemic conditions may play a significant role in worsening stroke outcomes due to microbiome dysbiosis. CONCLUSION: Recent research has illuminated the vital role of the GBA in propagating poor clinical outcomes, such as hemorrhagic transformation, following ischemic stroke. Considering this detrimental consequence of stroke, and the apparent role of the GBA role, future therapeutics should aim to mitigate this peripheral contribution to stroke complications.

Contemplating IL-6, a double-edged sword cytokine: Which side to use for stroke pathology?

Interleukin (IL)-6 is a unique cytokine due to its dual signaling, with one pathway being pro-inflammatory (trans) and the other homeostatic (classical). Both of these pathways have been implicated in neuroinflammation following stroke, with initial inflammatory mechanisms being protective and later anti-inflammatory signaling promoting ischemic tissue recovery. IL-6 plays a major role in stroke pathology. However, given these distinctive IL-6 signaling consequences, IL-6 is a difficult cytokine to target for stroke therapies. Recent research suggests that the ratio between the pro-inflammatory binary IL6:sIL6R complex and the inactive ternary IL6:sIL6R:sgp130 complex may be a novel way to measure IL-6 signaling at different time points following ischemic injury. This ratio may approximate functional consequences on individualized stroke therapies, allowing clinicians to determine whether IL-6 agonists or antagonists should be used at specific time points.

O-Arm Accuracy and Radiation Exposure in Adult Deformity Surgery.

OBJECTIVE: In long thoracolumbar deformity surgery, accurate screw positioning is critical for spinal stability. We assessed pedicle and pelvic screw accuracy and radiation exposure in patients undergoing long thoracolumbar deformity fusion surgery (≥4 levels) involving 3-dimensional fluoroscopy (O-Arm/Stealth) navigation. METHODS: In this retrospective single-center cohort study, all patients aged >18 years who underwent fusion in 2016-2018 were reviewed. O-Arm images were assessed for screw accuracy. Effective radiation doses were calculated. The primary outcome was pedicle screw accuracy (Heary grade). Secondary outcomes were pelvic fixation screw accuracy, radiation exposure, and screw-related perioperative and postoperative complications or revision surgery within 3 years. RESULTS: Of 1477 pedicle screws placed in 91 patients (mean 16.41 ± 5.6 screws/patient), 1208 pedicle screws (81.8%) could be evaluated by 3-dimensional imaging after placement. Heary Grade I placement was achieved in 1150 screws (95.2%), Grade II in 47 (3.9%), Grade III in 10 (0.82%), Grade IV in 1 (0.08%), and Grade V in 0; Grade III-V were replaced intraoperatively. One of 60 (1.6%) sacroiliac screws placed showed medial cortical breach and was replaced. The average O-Arm-related effective dose was 29.54 ± 14.29 mSv and effective dose/spin was 8.25 ± 2.65 mSv. No postoperative neurological worsening, vascular injuries, or revision surgeries for screw misplacement were recorded. CONCLUSIONS: With effective radiation doses similar to those in interventional neuroendovascular procedures, the use of O-Arm in multilevel complex deformity surgery resulted in high screw accuracy, no need for surgical revision because of screw malposition, less additional imaging, and no radiation exposure for the surgical team.

Multispectral fluorine-19 MRI enables longitudinal and noninvasive monitoring of tumor-associated macrophages.

High-grade gliomas, the most common and aggressive primary brain tumors, are characterized by a complex tumor microenvironment (TME). Among the immune cells infiltrating the glioma TME, tumor-associated microglia and macrophages (TAMs) constitute the major compartment. In patients with gliomas, increased TAM abundance is associated with more aggressive disease. Alterations in TAM phenotypes and functions have been reported in preclinical models of multiple cancers during tumor development and after therapeutic interventions, including radiotherapy and molecular targeted therapies. These findings indicate that it is crucial to evaluate TAM abundance and dynamics over time. Current techniques to quantify TAMs in patients rely mainly on histological staining of tumor biopsies. Although informative, these techniques require an invasive procedure to harvest the tissue sample and typically only result in a snapshot of a small region at a single point in time. Fluorine isotope 19 MRI (19F MRI) represents a powerful means to noninvasively and longitudinally monitor myeloid cells in pathological conditions by intravenously injecting perfluorocarbon-containing nanoparticles (PFC-NP). In this study, we demonstrated the feasibility and power of 19F MRI in preclinical models of gliomagenesis, breast-to-brain metastasis, and breast cancer and showed that the major cellular source of 19F signal consists of TAMs. Moreover, multispectral 19F MRI with two different PFC-NP allowed us to identify spatially and temporally distinct TAM niches in radiotherapy-recurrent murine gliomas. Together, we have imaged TAMs noninvasively and longitudinally with integrated cellular, spatial, and temporal resolution, thus revealing important biological insights into the critical functions of TAMs, including in disease recurrence.

L4 Corpectomy: Surgical Approaches and Mitigating the Risk of Femoral Nerve Injuries.

OBJECTIVE: Because of the challenging anatomic location, corpectomies are performed less often at the fourth lumbar vertebral body than at other levels. Our objective was to review the literature of L4 corpectomy and anterior column reconstruction. METHODS: A literature search in the Medline/PubMed database was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines to identify all relevant cases and cases series describing corpectomies of the L4 vertebral body using "lumbar" AND "corpectomy" as search terms. We present an illustrative case to describe the technique. RESULTS: We identified 18 articles with 30 patients who met the search criteria. Including our case illustration, the most common approach used was the lateral retroperitoneal approach (n = 17, 54.8%), of which 8 (26.7%) were performed via a transpsoas approach. Seven (23%) patients underwent corpectomy through a posterior approach, 4 (12.9%) through an anterior retroperitoneal approach, and 3 (10%) through combined anterior and lateral retroperitoneal. The overall complications rate was 19.3% including 1 case each of femoral nerve injury and iatrogenic lumbar nerve root injury. CONCLUSIONS: Corpectomies of the L4 vertebral body are challenging. None of the various approaches described clearly demonstrates any superiority in mitigating the risk of neural complications. Decision making about which surgical approach to use should be based on patient-specific characteristics.

Multimodal imaging of the dynamic brain tumor microenvironment during glioblastoma progression and in response to treatment.

Tumors evolve in a dynamic communication with their native tissue environment and recruited immune cells. The diverse components of the tumor microenvironment (TME) can critically regulate tumor progression and therapeutic response. In turn, anticancer treatments may alter the composition and functions of the TME. To investigate this continuous dialog in the context of primary brain cancers, we developed a multimodal longitudinal imaging strategy. We combined macroscopical magnetic resonance imaging with subcellular resolution two-photon intravital microscopy, and leveraged the power of single-cell analysis tools to gain insights into the ongoing interactions between different components of the TME and cancer cells. Our experiments revealed that the migratory behavior of tumor-associated macrophages is different in genetically distinct glioblastomas, and in response to macrophage-targeted therapy. These results underscore the importance of studying cancer longitudinally in an in vivo setting, to reveal complex and dynamic alterations in the TME during disease progression and therapeutic intervention.

Microclots in subarachnoid hemorrhage: an underestimated factor in delayed cerebral ischemia?

Subarachnoid hemorrhage has a poor prognosis due to the wide array of associated complications such as vasospasm, early brain injury, cortical spreading depression, oxidative stress, inflammation, and apoptosis. Each of these complications increases the risk of delayed cerebral ischemia (DCI), but recent research has suggested microclots play a substantial role in DCI incidence. This review will focus on the underlying inflammatory and coagulative mechanisms of microthrombosis while also outlining the current literature relating microclot burden to DCI. With a better understanding DCI pathophysiology as it relates to microthrombosis, more effective therapies can be developed in the future to improve clinical outcomes of SAH.

The role of IL-6 in TBI and PTSD, a potential therapeutic target?

This literature review focuses on the role of IL-6 in TBI or PTSD-induced neuroinflammation. While TBI and PTSD are widely prevalent, these diagnoses are particularly common amongst veterans. Given the role of IL-6 in neuroprotection acutely, compared to detrimental chronically, targeting this cytokine at specific time points may be beneficial in modulating neuroinflammation. Current treatments for TBI or PTSD are variably affective. By reviewing the role of IL-6 in these two diagnoses, future studies can focus on therapeutics to treat neuroinflammation and ultimately reduce the devastating impacts of neuroinflammation on cognition in PTSD and TBI.

Differences in postoperative quality of life in young, early elderly, and late elderly patients undergoing surgical treatment for degenerative cervical myelopathy.

OBJECTIVE: Cervical spondylotic myelopathy (CSM) is a common progressive spine disorder affecting predominantly middle-aged and elderly populations. With increasing life expectancy, the incidence of CSM is expected to rise further. The outcomes of elderly patients undergoing CSM surgery and especially their quality of life (QOL) postoperatively remain undetermined. This study retrospectively reviewed patients to identify baseline differences and validated postoperative patient-reported outcome (PRO) measures in elderly patients undergoing CSM surgery. METHODS: The multi-institutional, neurosurgery-specific NeuroPoint Quality Outcomes Database was queried to identify CSM patients treated surgically at the 14 highest-volume sites from January 2016 to December 2018. Patients were divided into three groups: young (< 65 years), early elderly (65-74 years), and late elderly (≥ 75 years). Demographic and PRO measures (Neck Disability Index [NDI] score, modified Japanese Orthopaedic Association [mJOA] score, EQ-5D score, EQ-5D visual analog scale [VAS] score, arm pain VAS, and neck pain VAS) were compared among the groups at baseline and 3 and 12 months postoperatively. RESULTS: A total of 1151 patients were identified: 691 patients (60%) in the young, 331 patients (28.7%) in the early elderly, and 129 patients (11.2%) in the late elderly groups. At baseline, younger patients presented with worse NDI scores (p < 0.001) and lower EQ-5D VAS (p = 0.004) and EQ-5D (p < 0.001) scores compared with early and late elderly patients. No differences among age groups were found in the mJOA score. An improvement of all QOL scores was noted in all age groups. On unadjusted analysis at 3 months, younger patients had greater improvement in arm pain VAS, NDI, and EQ-5D VAS compared with early and late elderly patients. At 12 months, the same changes were seen, but on adjusted analysis, there were no differences in PROs between the age groups. CONCLUSIONS: The authors' results indicate that elderly patients undergoing CSM surgery achieved QOL outcomes that were equivalent to those of younger patients at the 12-month follow-up.