Socioeconomic Disparities Affecting the Presentation and Outcomes in Pediatric Subdural Empyema Patients.

BACKGROUND AND OBJECTIVES: Pediatric subdural empyemas (SDE) carry significant morbidity and mortality, and prompt diagnosis and treatment are essential to ensure optimal outcomes. Nonclinical factors affect presentation, time to diagnosis, and outcomes in several neurosurgical conditions and are potential causes of delay in presentation and treatment for patients with SDE. To evaluate whether socioeconomic status, race, and insurance status affect presentation, time to diagnosis, and outcomes for children with subdural empyema. METHODS: We conducted a retrospective cohort study with patients diagnosed with SDE between 2005 and 2020 at our institution. Information regarding demographics (age, sex, zip code, insurance status, race/ethnicity) and presentation (symptoms, number of prior visits, duration of symptoms) was collected. Outcome measures included mortality, postoperative complications, length of stay, and discharge disposition. RESULTS: 42 patients were diagnosed with SDE with a mean age of 9.5 years. Most (85.7%) (n = 36) were male ( P = .0004), and a majority, 28/42 (66.7%), were African American ( P < .0001). There was no significant difference in socioeconomic status based on zip codes, although a significantly higher number of patients were on public insurance ( P = .015). African American patients had a significantly longer duration of symptoms than their Caucasian counterparts (8.4 days vs 1.8 days P = .0316). In total, 41/42 underwent surgery for the SDE, most within 24 hours of initial neurosurgical evaluation. There were no significant differences in the average length of stay. The average length of antibiotic duration was 57.2 days and was similar for all patients. There were no significant differences in discharge disposition based on any of the factors identified with most of the patients (52.4%) being discharged to home. There was 1 mortality (2.4%). CONCLUSION: Although there were no differences in outcomes based on nonclinical factors, African American men on public insurance bear a disproportionately high burden of SDE. Further investigation into the causes of this is warranted.

Neurosurgical management of patients with Ehlers-Danlos syndrome: A descriptive case series.

Introduction: Ehlers-Danlos syndrome (EDS) is a connective tissue disorder that has been linked to several neurological problems including Chiari malformations, atlantoaxial instability (AAI), craniocervical instability (CCI), and tethered cord syndrome. However, neurosurgical management strategies for this unique population have not been well-explored to date. The purpose of this study is to explore cases of EDS patients who required neurosurgical intervention to better characterize the neurological conditions they face and to better understand how neurosurgeons should approach the management of these patients. Methods: A retrospective review was done on all patients with a diagnosis of EDS who underwent a neurosurgical operation with the senior author (FAS) between January 2014 and December 2020. Demographic, clinical, operative, and outcome data were collected, with additional radiographic data collected on patients chosen as case illustrations. Results: Sixty-seven patients were identified who met the criteria for this study. The patients experienced a wide array of preoperative diagnoses, with Chiari malformation, AAI, CCI, and tethered cord syndrome representing the majority. The patients underwent a heterogeneous group of operations with the majority including a combination of the following procedures- suboccipital craniectomy, occipitocervical fusion, cervical fusion, odontoidectomy, and tethered cord release. The vast majority of patients experienced subjective symptomatic relief from their series of procedures. Conclusions: EDS patients are prone to instability, especially in the occipital-cervical region, which may predispose these patients to require a higher rate of revision procedures and may require modifications in neurosurgical management that should be further explored.

CCR5 deficiency normalizes TIMP levels, working memory, and gamma oscillation power in APOE4 targeted replacement mice.

The APOE4 allele increases the risk for Alzheimer's disease (AD) in a dose-dependent manner and is also associated with cognitive decline in non-demented elderly controls. In mice with targeted gene replacement (TR) of murine APOE with human APOE3 or APOE4, the latter show reduced neuronal dendritic complexity and impaired learning. APOE4 TR mice also show reduced gamma oscillation power, a neuronal population activity which is important to learning and memory. Published work has shown that brain extracellular matrix (ECM) can reduce neuroplasticity as well as gamma power, while attenuation of ECM can instead enhance this endpoint. In the present study we examine human cerebrospinal fluid (CSF) samples from APOE3 and APOE4 individuals and brain lysates from APOE3 and APOE4 TR mice for levels of ECM effectors that can increase matrix deposition and restrict neuroplasticity. We find that CCL5, a molecule linked to ECM deposition in liver and kidney, is increased in CSF samples from APOE4 individuals. Levels of tissue inhibitor of metalloproteinases (TIMPs), which inhibit the activity of ECM-degrading enzymes, are also increased in APOE4 CSF as well as astrocyte supernatants brain lysates from APOE4 TR mice. Importantly, as compared to APOE4/wild-type heterozygotes, APOE4/CCR5 knockout heterozygotes show reduced TIMP levels and enhanced EEG gamma power. The latter also show improved learning and memory, suggesting that the CCR5/CCL5 axis could represent a therapeutic target for APOE4 individuals.

Subdural evacuation port system and middle meningeal artery embolization for chronic subdural hematoma: a multicenter experience.

OBJECTIVE: Middle meningeal artery (MMA) embolization and the Subdural Evacuation Port System (SEPS) are minimally invasive treatment paradigms for chronic subdural hematoma (cSDH). Although SEPS offers acute decompression of local mass effect from a cSDH, MMA embolization has been shown to reduce the rate of cSDH recurrence. In combination, these procedures present a potentially safer strategy to a challenging pathology. The authors present a multi-institutional retrospective case series that assessed the safety, efficacy, and complications of SEPS and MMA embolization for cSDH. METHODS: A retrospective review was performed of patients who underwent SEPS placement and MMA embolization for cSDH between 2018 and 2021 at three institutions. RESULTS: One hundred patients with 136 cSDHs and a median age of 73 years underwent both SEPS placement and MMA embolization. Initial Glasgow Coma Scale scores were between 14 and 15 in 81% of patients and between 9 and 13 in 14%. The median initial midline shift (MLS) was 7 mm, with subdural hematoma (SDH) in the left hemisphere (lh) in 30% of patients, right hemisphere (rh) in 34%, and bilateral hemispheres in 36%. Follow-up was available for 86 patients: 93.4% demonstrated decreased MLS, and all patients with lhSDH and rhSDH demonstrated progressive decrease in SDH size. The overall complication rate was 4%, including 1 case of facial palsy and 3 cases of iatrogenic acute SDH. Two subjects (2%) required craniotomy for hematoma evacuation. The rate of good functional outcomes, with modified Rankin Scale (mRS) score < 2, was 89% on final follow-up and the overall mortality rate was 2%. A good mRS score on admission was associated with increased odds of functional improvement at follow-up (p < 0.001). CONCLUSIONS: SEPS placement with MMA embolization for cSDH can be done safely and effectively reduces cSDH size with minimal perioperative morbidity.

Awake transradial middle meningeal artery embolization and twist drill craniostomy for chronic subdural hematomas in the elderly: case series and technical note.

BACKGROUND: Due to prohibitive perioperative risk factors, optimal treatment for chronic subdural hematomas (cSDH) in the elderly remains unclear. Minimally invasive techniques are a viable option and include bedside subdural evacuation port system (SEPS), as well as prevention of recurrence with middle meningeal artery (MMA) embolization. We present a case series of elderly patients undergoing combined transradial MMA embolization and bed-side craniostomy as primary treatment for cSDH. METHODS: Patients 70 years and older from 2019 to 2020 that underwent single setting, awake transradial MMA embolization with concurrent SEPS placement under local anesthesia were included. Those with prior treatments, interventions performed under general anesthesia, or with less than 60-day follow-up were excluded. Descriptive analyses of baseline characteristics, radiologic parameters, comorbidities, and outcome measures were completed. RESULTS: Twenty elderly patients (mean age of 81.0 years) with multiple comorbidities underwent 28 MMA embolization+SEPS procedures as primary treatment for cSDH. Mean cSDH thickness was 1.8cm±0.6 cm with 7.3±3.9 mm midline shift. All patients tolerated the procedure well. 1/20 (5.0%) patients died within 30 days of the procedure. A majority of patients were discharged to home (12/20; 60.0%). There was an average of 3.6-month follow-up and one patient (5.0%) developed recurrence in the follow-up period requiring further intervention. CONCLUSIONS: In select elderly patients with high perioperative risk factors, primary treatment of cSDH using awake transradial MMA embolization+SEPS placement is a minimally invasive, feasible, and safe option. Further comparative studies are warranted to evaluate efficacy of the treatment.

Targeting protein arginine methyltransferase 5 sensitizes glioblastoma to trametinib.

Background: The prognosis of glioblastoma (GBM) remains dismal because therapeutic approaches have limited effectiveness. A new targeted treatment using MEK inhibitors, including trametinib, has been proposed to improve GBM therapy. Trametinib had a promising preclinical effect against several cancers, but its adaptive treatment resistance precluded its clinical translation in GBM. Previously, we have demonstrated that protein arginine methyltransferase 5 (PRMT5) is upregulated in GBM and its inhibition promotes apoptosis and senescence in differentiated and stem-like tumor cells, respectively. We tested whether inhibition of PRMT5 can enhance the efficacy of trametinib against GBM. Methods: Patient-derived primary GBM neurospheres (GBMNS) with transient PRMT5 knockdown were treated with trametinib and cell viability, proliferation, cell cycle progression, ELISA, and western blot were analyzed. In vivo, NSG mice were intracranially implanted with PRMT5-intact and -depleted GBMNS, treated with trametinib by daily oral gavage, and observed for tumor progression and mice survival rate. Results: PRMT5 depletion enhanced trametinib-induced cytotoxicity in GBMNS. PRMT5 knockdown significantly decreased trametinib-induced AKT and ERBB3 escape pathways. However, ERBB3 inhibition alone failed to block trametinib-induced AKT activity suggesting that the enhanced antitumor effect imparted by PRMT5 knockdown in trametinib-treated GBMNS resulted from AKT inhibition and not ERBB3 inhibition. In orthotopic murine xenograft models, PRMT5-depletion extended the survival of tumor-bearing mice, and combination with trametinib further increased survival. Conclusion: Combined PRMT5/MEK inhibition synergistically inhibited GBM in animal models and is a promising strategy for GBM therapy.

Treatment of chronic subdural hematoma in a patient with a left ventricular assist device: Case report and review of the literature.

Patients with left ventricular assist devices (LVADs) provide a unique challenge with regard to the management of subdural hematomas (SDH), due to preexisting comorbidities and induced coagulopathy. We report on the case of a 63-year-old female with a preexisting LVAD who developed an acute on chronic SDH with 15 mm of midline shift. She was successfully treated with middle meningeal artery (MMA) embolization and placement of a bedside subdural evacuating port system without hematoma recurrence at 1-year follow-up. Both operative and nonoperative management of SDHs in patients with LVAD is associated with high risk of mortality and morbidity. Chronic SDHs in this patient population can be successfully managed with a minimally invasive approach that includes MMA embolization and bedside subdural drain placement.

Craniocervical Stabilization After Failed Chiari Decompression: A Case Series of a Population with High Prevalence of Ehlers-Danlos Syndrome.

BACKGROUND: In the treatment of Chiari malformation type I (CM-I), posterior fossa decompression is achieved via suboccipital craniectomy (SOC); however, some patients continue to experience symptoms after treatment, which may be due to craniocervical instability (CCI). The purposes of this study were to analyze data from patients who required an occipitocervical fusion (OCF) for the management of CCI after having previously undergone SOC for CM-I to determine if OCF is a safe and effective option and to determine any identifiable risk factors for CCI in these patients. METHODS: A retrospective review was done on all patients who underwent an OCF performed by the senior author between November 2013 and June 2020 after having previously undergone SOC for CM-I. Demographic, radiographic, perioperative, and outcome data were collected and clivoaxial angles (CXAs) were measured pre- and postoperatively. RESULTS: Fifteen patients were identified who developed symptomatic CCI after previously undergoing a suboccipital craniectomy for the treatment of CM-I. All 15 patients were treated by OCF with good outcome. Of these, 12 patients had a known diagnosis of Ehlers-Danlos syndrome (EDS). Overall, the CXAs of these patients were found to be corrected to a more anatomical alignment. CONCLUSIONS: Symptomatic CCI should be recognized as a delayed postoperative complication in the surgical treatment of CM-I, with an underlying connective tissue hypermobility disorder such as EDS serving as a potential risk factor its development. CCI can be managed with OCF as a safe and effective treatment option for this patient population.

Minimally invasive surgery for intradural extramedullary spinal cord pathologies: A case series and technical note.

BACKGROUND: Intradural spinal cord pathologies have traditionally been managed with open surgical procedures and require the completion of a durotomy. Minimally invasive techniques are emerging as alternative procedures with the goal of reducing complications, but often require specialized equipment with additional training. METHODS: We conduct a single institution retrospective review from 2016 to 2019 of patients undergoing minimally invasive durotomy closure for intradural extramedullary pathologies using a novel technique that utilizes standard operating room equipment. This cohort is compared to a cohort of patients treated with a traditional open approach. RESULTS: Patients treated with minimally invasive surgery (MIS) had no statistically significant differences in baseline characteristics compared to patients treated with open procedures. Patients treated with MIS had decreases in complication rates, estimated blood loss, and length of stay in the hospital compared to the patients treated with open procedures, but these differences did not reach levels of statistical significance. CONCLUSIONS: Our novel MIS technique for intradural extramedullary pathologies appears to be safe and effective in creating a watertight dural closure using standard operating room equipment, while avoiding the costs and training associated with specialized equipment and possibly improving surgical outcome measures when compared to open approaches.

Middle meningeal artery embolization with subdural evacuating port system for primary management of chronic subdural hematomas.

Optimal treatment for chronic subdural hematomas remains controversial and perioperative risks and comorbidities may affect management strategies. Minimally invasive procedures are emerging as alternatives to the standard operative treatments. We evaluate our experience with middle meningeal artery (MMA) embolization combined with Subdural Evacuating Port System (SEPS) placement as a first-line treatment for patients with cSDH. A single institution retrospective review was performed of all patients undergoing intervention. Patients were stratified by treatment with MMA embolization and SEPS placement, MMA embolization and surgery, SEPS placement only, and surgery only for cSDH from 2017 to 2020, and cohorts were compared against each other. Patients treated with MMA/SEPS were more likely to be older, be on anticoagulation, have significant comorbidities, have shorter length of stay, and less likely to have symptomatic recurrence compared to SEPS only cohort. Thus, MMA/SEPS appears to be a safe and equally effective minimally invasive treatment for cSDH patients with significant comorbidities who are poor surgical candidates.