Hemoglobin Drop is Associated with Early Post-operative Stroke Following Revascularization Surgery for Moyamoya Disease.

BACKGROUND: Postoperative stroke is a potentially devastating neurological complication following surgical revascularization for Moyamoya disease. We sought to evaluate whether peri-operative hemoglobin levels were associated with the risk of early post-operative stroke following revascularization surgery in adult Moyamoya patients. METHODS: Adult patients having revascularization surgeries for Moyamoya disease between 1999-2022 were identified through single institutional retrospective review. Logistic regression analysis was used to test for the association between hemoglobin drop and early postoperative stroke. RESULTS: In all, 106 revascularization surgeries were included in the study. A stroke occurred within 7 days after surgery in 9.4% of cases. There were no significant associations between the occurrence of an early postoperative stroke and patient age, gender, or race. Mean postoperative hemoglobin drop was greater in patients who suffered an early postoperative stroke compared with patients who did not (2.3±1.1 g/dL vs. 1.3±1.1 g/dL, respectively; P=0.034). Patients who experienced a hemoglobin drop post-operatively had 2.03 times greater odds (95% confidence interval, 1.06-4.23; P=0.040) of having a stroke than those whose hemoglobin levels were stable. Early postoperative stroke was also associated with an increase in length of hospital stay (P<0.001), discharge to a rehabilitation facility (P=0.014), and worse modified Rankin scale at 1 month (P=0.001). CONCLUSION: This study found a significant association between hemoglobin drop and early postoperative stroke following revascularization surgery in adult patients with Moyamoya disease. Based on our findings, it may be prudent to avoid hemoglobin drops in Moyamoya patients undergoing surgical revascularization.

External assessment of preoperative scores for predicting outcome after microvascular decompression for trigeminal neuralgia.

OBJECTIVE: Recently, two scoring systems have been developed for predicting pain-free outcomes after microvascular decompression (MVD). Evaluation of these scores on large external datasets has been limited. In this study, the authors aimed to evaluate the performance of published MVD scoring systems in predicting pain-free outcome. METHODS: A total of 458 patients who underwent MVD for trigeminal neuralgia (TN) between 2007 and 2020 and had at least 6 months of follow-up were included in this study. Hardaway and Panczykowski scores were retrospectively computed for each patient and compared with postoperative pain recurrence and pain-free duration. RESULTS: The mean ± SD area under the receiver operating characteristic curve for predicting any pain recurrence after MVD was 0.567 ± 0.081 using the Hardaway score and 0.546 ± 0.085 using the Panczykowski score. On log-rank tests and Kaplan-Meier analysis, the patients with Hardaway scores of 0-2 had significantly shorter pain-free survival times after MVD than did those with a score of 3. Patients with a Panczykowski score of 1 had a significantly shorter pain-free duration after surgery compared with both patients with scores of 2-3 and patients with scores of 4-5. Patients with Panczykowski scores of 2-3 also had significantly shorter pain-free duration compared with patients with scores of 4-5. CONCLUSIONS: Both the Hardaway and Panczykowski scores may be useful for predicting postoperative pain-free duration in TN patients, and their utility may be greatest when scores are clustered. Continued refinement of both scoring systems will help to improve our ability to predict patient outcomes after MVD.

Preoperative Opioid Use and Postoperative Outcomes in Patients Undergoing Microvascular Decompression for Trigeminal Neuralgia.

BACKGROUND AND OBJECTIVES: The prescription of opioid analgesics for trigeminal neuralgia (TN) is controversial, and their effect on postoperative outcomes for patients with TN undergoing microvascular decompression (MVD) has not been reported. We aimed to describe the relationship between preoperative opioid use and postoperative outcomes in patients with TN undergoing MVD. METHODS: We reviewed the records of 920 patients with TN at our institution who underwent an MVD between 2007 and 2020. Patients were sorted into 2 groups based on preoperative opioid usage. Demographic information, comorbidities, characteristics of TN, preoperative medications, pain and numbness outcomes, and recurrence data were recorded and compared between groups. Multivariate ordinal regression, Kaplan-Meier survival analysis, and Cox proportional hazards were used to assess differences in pain outcomes between groups. RESULTS: One hundred and forty-five (15.8%) patients in this study used opioids preoperatively. Patients who used opioids preoperatively were younger (P = .04), were more likely to have a smoking history (P < .001), experienced greater pain in modified Barrow Neurological Institute pain score at final follow-up (P = .001), and were more likely to experience pain recurrence (P = .01). In addition, patients who used opioids preoperatively were more likely to also have been prescribed TN medications including muscle relaxants and antidepressants preoperatively (P < .001 and P < .001, respectively). On multivariate regression, opioid use was an independent risk factor for greater postoperative pain at final follow-up (P = .006) after controlling for variables including female sex and age. Opioid use was associated with shorter time to pain recurrence on Kaplan-Meier analysis (P = .005) and was associated with increased risk for recurrence on Cox proportional hazards regression (P = .008). CONCLUSION: Preoperative opioid use in the setting of TN is associated with worse pain outcomes and increased risk for pain recurrence after MVD. These results indicate that opioids should be prescribed cautiously for TN and that worse post-MVD outcomes may occur in patients using opioids preoperatively.

Soluble PD-L1 reprograms blood monocytes to prevent cerebral edema and facilitate recovery after ischemic stroke.

Acute cerebral ischemia triggers a profound inflammatory response. While macrophages polarized to an M2-like phenotype clear debris and facilitate tissue repair, aberrant or prolonged macrophage activation is counterproductive to recovery. The inhibitory immune checkpoint Programmed Cell Death Protein 1 (PD-1) is upregulated on macrophage precursors (monocytes) in the blood after acute cerebrovascular injury. To investigate the therapeutic potential of PD-1 activation, we immunophenotyped circulating monocytes from patients and found that PD-1 expression was upregulated in the acute period after stroke. Murine studies using a temporary middle cerebral artery (MCA) occlusion (MCAO) model showed that intraperitoneal administration of soluble Programmed Death Ligand-1 (sPD-L1) significantly decreased brain edema and improved overall survival. Mice receiving sPD-L1 also had higher performance scores short-term, and more closely resembled sham animals on assessments of long-term functional recovery. These clinical and radiographic benefits were abrogated in global and myeloid-specific PD-1 knockout animals, confirming PD-1+ monocytes as the therapeutic target of sPD-L1. Single-cell RNA sequencing revealed that treatment skewed monocyte maturation to a non-classical Ly6Clo, CD43hi, PD-L1+ phenotype. These data support peripheral activation of PD-1 on inflammatory monocytes as a therapeutic strategy to treat neuroinflammation after acute ischemic stroke.

Awake Versus Asleep Craniotomy for Patients With Eloquent Glioma: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Awake vs asleep craniotomy for patients with eloquent glioma is debatable. This systematic review and meta-analysis sought to compare awake vs asleep craniotomy for the resection of gliomas in the eloquent regions. METHODS: MEDLINE and PubMed were searched from inception to December 13, 2022. Primary outcomes were the extent of resection (EOR), overall survival (month), progression-free survival (month), and rates of neurological deficit, Karnofsky performance score, and seizure freedom at the 3-month follow-up. Secondary outcomes were duration of operation (minute) and length of hospital stay (LOS) (day). RESULTS: Fifteen studies yielded 2032 patients, from which 800 (39.4%) and 1232 (60.6%) underwent awake and asleep craniotomy, respectively. The meta-analysis concluded that the awake group had greater EOR (mean difference [MD] = MD = 8.52 [4.28, 12.76], P < .00001), overall survival (MD = 2.86 months [1.35, 4.37], P = .0002), progression-free survival (MD = 5.69 months [0.75, 10.64], P = .02), 3-month postoperative Karnofsky performance score (MD = 13.59 [11.08, 16.09], P < .00001), and 3-month postoperative seizure freedom (odds ratio = 8.72 [3.39, 22.39], P < .00001). Furthermore, the awake group had lower 3-month postoperative neurological deficit (odds ratio = 0.47 [0.28, 0.78], P = .004) and shorter LOS (MD = -2.99 days [-5.09, -0.88], P = .005). In addition, the duration of operation was similar between the groups (MD = 37.88 minutes [-34.09, 109.86], P = .30). CONCLUSION: Awake craniotomy for gliomas in the eloquent regions benefits EOR, survival, postoperative neurofunctional outcomes, and LOS. When feasible, the authors recommend awake craniotomy for surgical resection of gliomas in the eloquent regions.

Perioperative Infection After Aneurysmal Subarachnoid Hemorrhage: Risk Factors, Causative Pathogens, and Long-Term Outcomes.

BACKGROUND AND OBJECTIVES: Nosocomial infections are the most common complication among critically ill patients and contribute to poor long-term outcomes. Patients with aneurysmal subarachnoid hemorrhage (aSAH) are highly susceptible to perioperative infections, yet it is unclear what factors influence infection onset and functional recovery. The objective was to investigate risk factors for perioperative infections after aSAH and relate causative pathogens to patient outcomes. METHODS: Clinical records were obtained for 194 adult patients with aSAH treated at our institution from 2016 to 2020. Demographics, clinical course, complications, microbiological reports, and outcomes were collected. χ 2 , univariate, and multivariate logistic regression analyses were used to analyze risk factors. RESULTS: Nearly half of the patients developed nosocomial infections, most frequently pneumonia and urinary tract infection. Patients with infections had longer hospital stays, higher rates of delayed cerebral ischemia, and worse functional recovery up to 6 months after initial hemorrhage. Independent risk factors for pneumonia included male sex, comatose status at admission, mechanical ventilatory use, and longer admission, while those for urinary tract infection included older age and longer admission. Staphylococcus , Klebsiella , and Enterococcus spp. were associated with poor long-term outcome. Certain pathogenic organisms were associated with delayed cerebral ischemia. CONCLUSION: Perioperative infections are highly prevalent among patients with aSAH and are related to adverse outcomes. The risk profiles for nosocomial infections are distinct to each infection type and causative organism. Although strong infection control measures should be universally applied, patient management must be individualized in the context of specific infections.

Hypothermia is Associated with Improved Neurological Outcomes After Mechanical Thrombectomy.

BACKGROUND: Acute ischemic stroke (AIS) is the second leading cause of death globally. Mechanical thrombectomy (MT) has improved patient prognosis but expedient treatment is still necessary to minimize anoxic injury. Lower intraoperative body temperature decreases cerebral oxygen demand, but the role of hypothermia in treatment of AIS with MT is unclear. METHODS: We retrospectively reviewed patients undergoing MT for AIS from 2014 to 2020 at our institution. Patient demographics, comorbidities, intraoperative parameters, and outcomes were collected. Maximum body temperature was extracted from minute-by-minute anesthesia readings, and patients with maximal temperature below 36°C were considered hypothermic. Risk factors were assessed by χ2 and multivariate ordinal regression. RESULTS: Of 68 patients, 27 (40%) were hypothermic. There was no significant association of hypothermia with patient age, comorbidities, time since last known well, number of passes intraoperatively, favorable revascularization, tissue plasminogen activator use, and immediate postoperative complications. Hypothermic patients exhibited better neurologic outcome at 3-month follow-up (P = 0.02). On multivariate ordinal regression, lower maximum intraoperative body temperature was associated with improved 3-month outcomes (P < 0.001), when adjusting for other factors influencing neurological outcomes. Other significant protective factors included younger age (P = 0.03), better revascularization (P = 0.03), and conscious sedation (P = 0.02). CONCLUSIONS: Lower intraoperative body temperature during MT was independently associated with improved neurological outcome in this single center retrospective series. These results may help guide clinicians in employing therapeutic hypothermia during MT to improve long-term neurologic outcomes from AIS, although larger studies are needed.

Impact of Antithrombotic Medications and Reversal Strategies on the Surgical Management and Outcomes of Traumatic Acute Subdural Hematoma.

OBJECTIVE: Careful hematologic management is required in surgical patients with traumatic acute subdural hematoma (aSDH) taking antithrombotic medications. We sought to compare outcomes between patients with aSDH taking antithrombotic medications at admission who received antithrombotic reversal with patients with aSDH not taking antithrombotics. METHODS: Retrospective review identified patients with traumatic aSDH requiring surgical evacuation. The cohort was divided based on antithrombotic use and whether pharmacologic reversal agents or platelet transfusions were administered. A 3-way comparison of outcomes was performed between patients taking anticoagulants who received pharmacologic reversal, patients taking antiplatelets who received platelet transfusion, and patients not taking antithrombotics. Multivariable regressions, adjusted for injury severity, further investigated associations with outcomes. RESULTS: Of 138 patients who met inclusion criteria, 13.0% (n = 18) reported taking anticoagulants, 16.7% (n = 23) reported taking antiplatelets, and 3.6% (n = 5) reported taking both. Patients taking antiplatelets who received platelet transfusion had longer intraoperative times (P = 0.040) and higher rates of palliative care consultations (P = 0.046) compared with patients taking anticoagulants who received pharmacologic reversal and patients not taking antithrombotics. Across groups, no significant differences were found in frequency of in-hospital intracranial hemorrhage and venous thromboembolism, length of hospital stay, rate of inpatient mortality, or follow-up health status. In multivariable analysis, intraoperative time remained longest for the antiplatelets with platelet transfusion group. Other outcomes were not associated with patient group. CONCLUSIONS: Among surgical patients with traumatic aSDH, those taking antiplatelet medications who receive platelet transfusions experience longer intraoperative procedure times and higher rates of palliative care consultation. Comparable outcomes were observed between patients receiving antithrombotic reversal and patients not taking antithrombotics.

Craniotomy versus craniectomy for traumatic acute subdural hematoma-coarsened exact matched analysis of outcomes.

BACKGROUND AND OBJECTIVES: Acute subdural hematoma (aSDH) after traumatic brain injury frequently requires emergent craniotomy (CO) or decompressive craniectomy (DC). We sought to determine the variables associated with either surgical approach and to compare outcomes between matched patients. METHODS: A multi-center retrospective review was used to identify traumatic aSDH patients who underwent CO or DC. Patient variables independently associated with surgical approach were used for coarsened exact matching.Multivariate logistic regression and multivariate Cox proportional-hazards regression wereconducted on matched patients to determine independent predictors of mortality. RESULTS: Seventy-six patients underwent CO and sixty-two underwent DC for aSDH evacuation. DC patients were21.4 years younger (P < 0.001), more likely to be male (80.6 % vs 60.5 %,P = 0.011), and present with GCS ≤ 8 (64.5 % vs 36.8 %,P = 0.001). Age (P < 0.001), epidural hematoma (P = 0.01), skull fracture (P = 0.001), and cisternal effacement (P = 0.02) were independently associated with surgical approach. After coarsened exact matching, DC (P = 0.008), older age (P = 0.007), male sex (P = 0.04), and intraventricular hemorrhage (P = 0.02), were independently associated with inpatient mortality. Multivariate Cox proportional-hazards regression demonstrated that DC was independently associated with mortality at 90-days (P = 0.001) and 1-year post-operation (P = 0.003). CONCLUSION: aSDH patients who receive surgical evacuation via DC as opposed to CO are younger, more likely to be male, and have worse clinical exam. After controlling for patient differences via coarsened exact matching, DC is independently associated with mortality.

Risk of Subdural Hematoma Expansion in Patients With End-Stage Renal Disease: Continuous Venovenous Hemodialysis Versus Intermittent Hemodialysis.

BACKGROUND AND OBJECTIVES: Subdural hematoma (SDH) patients with end-stage renal disease (ESRD) require renal replacement therapy in addition to neurological management. We sought to determine whether continuous venovenous hemodialysis (CVVHD) or intermittent hemodialysis (iHD) is associated with higher rates of SDH re-expansion as well as morbidity and mortality. METHODS: Hemodialysis-dependent patients with ESRD who were discovered to have an SDH were retrospectively identified from 2016 to 2022. Rates of SDH expansion during CVVHD vs iHD were compared. Hemodialysis mode was included in a multivariate logistic regression model to test for independent association with SDH expansion and mortality. RESULTS: A total of 123 hemodialysis-dependent patients with ESRD were discovered to have a concomitant SDH during the period of study. Patients who received CVVHD were on average 10.2 years younger ( P < .001), more likely to have traumatic SDH (47.7% vs 19.0%, P < .001), and more likely to have cirrhosis (25.0% vs 10.1%, P = .029). SDH expansion affecting neurological function occurred more frequently during iHD compared with CVVHD (29.7% vs 12.0%, P = .013). Multivariate logistic regression analysis found that CVVHD was independently associated with decreased risk of SDH affecting neurological function (odds ratio 0.25, 95% CI 0.08-0.65). Among patients who experienced in-hospital mortality or were discharged to hospice, 5% suffered a neurologically devastating SDH expansion while on CVVHD compared with 35% on iHD. CONCLUSION: CVVHD was independently associated with decreased risk of neurologically significant SDH expansion. Therefore, receiving renal replacement therapy through a course of CVVHD may increase SDH stability in patients with ESRD.

Neurovascular Compression in Patients With Trigeminal Neuralgia May Be Associated With Worse Outcomes After Primary Percutaneous Rhizotomy.

BACKGROUND AND OBJECTIVES: Percutaneous rhizotomy may be an effective primary intervention in patients with trigeminal neuralgia who are poor candidates for microvascular decompression or those who desire a less invasive approach. However, the influence of neurovascular compression on pain-free survival after primary percutaneous rhizotomy is not well understood. METHODS: We retrospectively reviewed all patients undergoing percutaneous rhizotomy at our institution from 1995 to 2022. Patients were included if they had no history of surgical intervention, available preoperative MRI imaging, and postoperative follow-up data. Barrow Neurological Institute pain scores were assigned at various time points. We collected baseline patient information, pain characteristics, and perioperative complications for each patient. In addition, we recorded evidence of pain recurrence. Patients were dichotomized into those with evidence of neurovascular compression on preoperative MRI vs those without. The effect of neurovascular compression on pain-free survival was assessed using Kaplan-Meier Cox proportional hazards analyses. RESULTS: Of the 2726 patients reviewed, 298 met our inclusion criteria. Our study comprised 261 patients with no evidence of neurovascular compression on preoperative MRI vs 37 patients with evidence of neurovascular compression on preoperative MRI. Patients in the compression group had a shorter median duration to recurrence compared with those in the no compression group, P = .01. Kaplan-Meier survival analysis revealed that patients with preoperative evidence of neurovascular compression on MRI imaging demonstrated shorter pain-free survival compared with those without such evidence [hazard ratio = 1.57 (1.03-2.4), P = .037]. Cox proportional hazards analysis demonstrated that evidence of neurovascular compression was associated with poor pain-free survival [hazard ratio = 1.64 (1.06-2.53), P = .03]. CONCLUSION: Patients with neurovascular compression on preoperative MRI may experience reduced time to recurrence compared with those without after percutaneous rhizotomy. These patients should be counseled on potential reduced efficacy of percutaneous rhizotomy as a primary intervention for their pain.

The Role of γδ T-Lymphocytes in Glioblastoma: Current Trends and Future Directions.

Cell-based immunotherapy for glioblastoma (GBM) encounters major challenges due to the infiltration-resistant and immunosuppressive tumor microenvironment (TME). γδ T cells, unconventional T cells expressing the characteristic γδ T cell receptor, have demonstrated promise in overcoming these challenges, suggesting great immunotherapeutic potential. This review presents the role of γδ T cells in GBM and proposes several research avenues for future studies. Using the PubMed, ScienceDirect, and JSTOR databases, we performed a review of the literature studying the biology of γδ T cells and their role in GBM treatment. We identified 15 studies focused on γδ T cells in human GBM. Infiltrative γδ T cells can incite antitumor immune responses in certain TMEs, though rapid tumor progression and TME hypoxia may impact the extent of tumor suppression. In the studies, available findings have shown both the potential for robust antitumor activity and the risk of protumor activity. While γδ T cells have potential as a therapeutic agent against GBM, the technical challenges of extracting, isolating, and expanding γδ T cells, and the activation of antitumoral versus protumoral cascades, remain barriers to their application. Overcoming these limitations may transform γδ T cells into a promising immunotherapy in GBM.

Frailty Predicts Worse Pain Outcomes for Older TN Patients Treated with Microvascular Decompression.

BACKGROUND: Trigeminal neuralgia (TN) is a debilitating orofacial pain disorder. Recent data from a national database suggest that microvascular decompression (MVD) in frail patients is associated with more postoperative complications. However, the long-term pain outcomes for frail TN patients are not known. We aimed to elucidate the relationship between frailty and long-term pain outcomes after MVD for TN. METHODS: From 2007 to 2020, 368 TN patients aged ≥60 years underwent MVD at our institution. Patient demographics, clinical characteristics, postoperative complications, and long-term pain outcomes were recorded. Frailty was assessed using the modified 5-item frailty index (mFI-5) score, and the patients were dichotomized into nonfrail (mFI-5 <2) and frail (mFI-5 >1). Differences were assessed via the t test, χ2 test, multivariate ordinal regression, and Cox proportional hazards analysis. RESULTS: Of the 368 patients analyzed, 9.8% were frail. The frail patients were significantly older (P = 0.02) with a higher body mass index (P = 0.01) and a greater incidence of comorbidities (P < 0.001). Frail patients presented with significantly higher pain levels at the final follow-up (P = 0.04). On multivariate analysis, frailty was independently associated with more pain at follow-up (P = 0.01), as was younger age, female sex, and black race. The relationship between frailty and postoperative pain recurrence showed a trend toward significance (P = 0.06), and younger age and black race were significantly associated with recurrence. CONCLUSIONS: Frail patients undergoing MVD are at risk of worse long-term pain outcomes. Our results provide clinicians with useful information pertaining to the influence of frailty on the long-term efficacy of MVD in treating TN.

Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid.

It is often challenging to distinguish cancerous from non-cancerous lesions in the brain using conventional diagnostic approaches. We introduce an analytic technique called Real-CSF (repetitive element aneuploidy sequencing in CSF) to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) are PCR amplified with a single primer pair, and the PCR products are evaluated by next-generation sequencing. Real-CSF assesses genome-wide copy-number alterations as well as focal amplifications of selected oncogenes. Real-CSF was applied to 280 CSF samples and correctly identified 67% of 184 cancerous and 96% of 96 non-cancerous brain lesions. CSF analysis was considerably more sensitive than standard-of-care cytology and plasma cell-free DNA analysis in the same patients. Real-CSF therefore has the capacity to be used in combination with other clinical, radiologic, and laboratory-based data to inform the diagnosis and management of patients with suspected cancers of the brain.

Venous thromboembolism in aneurysmal subarachnoid hemorrhage: Risk factors and timing of chemoprophylaxis.

INTRODUCTION: Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality among patients recovering from aneurysmal subarachnoid hemorrhage (aSAH). Prophylactic heparin reduces the risk of VTE, but the optimal timing for its initiation among aSAH patients remains unclear. OBJECTIVE: To conduct a retrospective study assessing risk factors for VTE and optimal timing of chemoprophylaxis in patients treated for aSAH. METHODS: From 2016-2020, 194 adult patients were treated for aSAH at our institution. Patient demographics, clinical diagnoses, complications, pharmacologic interventions, and outcomes were recorded. Risk factors for symptomatic VTE (sVTE) were analyzed via Chi-squared, univariate, and multivariate regression. RESULTS: In total 33 patients presented with sVTE (25 DVT, 14 PE). Patients with sVTE had longer hospital stays (p < 0.01) and worse outcomes at one-month (p < 0.01) and three-month follow-up (p = 0.02). Univariate predictors of sVTE included male sex (p = 0.03), Hunt Hess score (p = 0.01), Glasgow Coma scale (p = 0.02), intracranial hemorrhage (p = 0.03), hydrocephalus requiring external ventricular drain (EVD) placement (p < 0.01), and mechanical ventilation (p < 0.01). Only hydrocephalus requiring EVD (p = 0.01) and ventilator use (p = 0.02) remained significant upon multivariate analysis. Patients with delayed heparin introduction were significantly more likely to sustain sVTE on univariate analysis (p = 0.02) with a trend-level significance on multivariate analysis (p = 0.07). CONCLUSIONS: Patients with aSAH are more likely to develop sVTE following use of perioperative EVD or mechanical ventilation. sVTE leads to longer hospital stays and worse outcomes among patients treated for aSAH. Delayed heparin initiation increases the risk of sVTE. Our results may help guide surgical decision-making during recovery from aSAH and improve VTE-related postoperative outcomes.

Use of tubular retractors to access deep brain lesions: A case series.

BACKGROUND: Deep-seated intracranial lesions can be accessed using blade retractors that may disrupt white matter tracts, exert pressure on adjacent tissue, and lead to post-operative venous injury. Tubular retractors may minimize disruption to white matter tracts by radially dispersing pressure onto surrounding tissue. This study characterizes perioperative outcomes in patients undergoing biopsy or resection of intracranial pathologies using tubular retractors. METHODS: Adult patients (≥18 years) undergoing neurosurgical intervention using tubular retractors at a single health system (January 2016-February 2022) were identified through chart review. Demographics, disease characteristics, management data, and clinical outcomes were collected. RESULTS: A total of 49 patients were included; 23 (47%) had primary brain tumors, 8 (16%) metastases, 6 (12%) intracranial hemorrhage (ICH), 5 (10%) cavernomas, and 7 (14%) other pathologies. Lesions were located subcortically (n = 19, 39%), intraventricularly (n = 15, 31%), and in deep gray matter (n = 11, 22%). Gross total resection (GTR) or near GTR was achieved in 21 of 26 (80.8%) patients with intracranial lesions where GTR was the goal of surgery; 10 of 11 (90.9%) biopsies in patients with masses were diagnostic. Five of six (83.3%) ICHs were totally or near totally evacuated. Seventeen patients (35%) had major complications post-operatively. The most common complications were DVT/PE (n = 7, 14%) and seizures (n = 6, 12%). For patients who experienced post-operative seizures, 3 had seizures preoperatively and 1 had seizures in the context of electrolyte derangements. No patients died of post-operative complications. CONCLUSION: This operative approach may facilitate safe and efficacious biopsy or resection of deep-seated intracranial pathologies.

No Delayed Ruptures on Long-Term Follow-Up of a Case Series of Persistently Filling Saccular Internal Carotid Artery Aneurysms After Flow Diversion With the Pipeline Embolization Device.

BACKGROUND AND OBJECTIVES: Flow diversion of intracranial aneurysms results in high occlusion rates. However, 10% to 20% remain persistently filling at 1 year. Often, these are retreated, but benefits of retreatment are not well established. A better understanding of the long-term rupture risk of persistently filling aneurysms after flow diversion is needed. METHODS: Our institutional database of 974 flow diversion cases was queried for persistently filling saccular aneurysms of the clinoidal, ophthalmic, and communicating segments of the internal carotid artery treated with the pipeline embolization device (PED, Medtronic). Persistent filling was defined as continued flow into the aneurysm on 1 year catheter angiogram. The clinical record was queried for retreatments and delayed ruptures. Clinical follow-up was required for at least 2 years. RESULTS: Ninety-four persistent aneurysms were identified. The average untreated aneurysm size was 5.6 mm. A branch vessel originated separately in 55% of cases from the body of the aneurysm in 10.6% of cases and from the neck in 34% of cases. Eighteen percent of aneurysms demonstrated >95% filling at 1 year, and 61% were filling 5% to 95% of their original size. The mean follow-up time was 4.9 years, including 41 cases with >5 years. No retreatment was undertaken in 91.5% of aneurysms. There were no cases of delayed subarachnoid hemorrhage. CONCLUSION: Among saccular internal carotid artery aneurysms treated with PED that demonstrated persistent aneurysm filling at 1 year, there were no instances of delayed rupture on long-term follow-up. These data suggest that observation may be appropriate for continued aneurysm filling at least in the first several years after PED placement.

Systematic elucidation and pharmacological targeting of tumor-infiltrating regulatory T cell master regulators.

Due to their immunosuppressive role, tumor-infiltrating regulatory T cells (TI-Tregs) represent attractive immuno-oncology targets. Analysis of TI vs. peripheral Tregs (P-Tregs) from 36 patients, across four malignancies, identified 17 candidate master regulators (MRs) as mechanistic determinants of TI-Treg transcriptional state. Pooled CRISPR-Cas9 screening in vivo, using a chimeric hematopoietic stem cell transplant model, confirmed the essentiality of eight MRs in TI-Treg recruitment and/or retention without affecting other T cell subtypes, and targeting one of the most significant MRs (Trps1) by CRISPR KO significantly reduced ectopic tumor growth. Analysis of drugs capable of inverting TI-Treg MR activity identified low-dose gemcitabine as the top prediction. Indeed, gemcitabine treatment inhibited tumor growth in immunocompetent but not immunocompromised allografts, increased anti-PD-1 efficacy, and depleted MR-expressing TI-Tregs in vivo. This study provides key insight into Treg signaling, specifically in the context of cancer, and a generalizable strategy to systematically elucidate and target MR proteins in immunosuppressive subpopulations.

CAR T Cell Therapy in Glioblastoma: Overcoming Challenges Related to Antigen Expression.

Glioblastoma (GBM) is the most common primary brain tumor, yet prognosis remains dismal with current treatment. Immunotherapeutic strategies have had limited effectiveness to date in GBM, but recent advances hold promise. One such immunotherapeutic advance is chimeric antigen receptor (CAR) T cell therapy, where autologous T cells are extracted and engineered to express a specific receptor against a GBM antigen and are then infused back into the patient. There have been numerous preclinical studies showing promising results, and several of these CAR T cell therapies are being tested in clinical trials for GBM and other brain cancers. While results in tumors such as lymphomas and diffuse intrinsic pontine gliomas have been encouraging, early results in GBM have not shown clinical benefit. Potential reasons for this are the limited number of specific antigens in GBM, their heterogenous expression, and their loss after initiating antigen-specific therapy due to immunoediting. Here, we review the current preclinical and clinical experiences with CAR T cell therapy in GBM and potential strategies to develop more effective CAR T cells for this indication.

Resection of Condylar Skull Base Tumor via Combined Far Lateral and Infrajugular Approaches with Single-Stage Occipitocervical Fusion.

Epithelioid hemangioma is a rare vascular mesenchymal tumor with a paucity of reports of cranial involvement. In particular, guidance on treatment for lateral skull base lesions is lacking, despite this being a highly technically challenging location. Nuances in the management decisions for this tumor type are discussed. Two major challenges with this location are proximity to critical neurovascular structures and managing secondary craniocervical instability. We present a patient with a lateral skull base epithelioid hemangioma treated with transcondylar resection, single-stage occipitocervical fusion, and adjuvant radiation and chemotherapy. The patient consented to both the procedure and the published report of her case including imaging. Obtaining tissue was necessary for diagnosis. Maximal safe resection, resection of a tumor such that the greatest clinical benefit is achieved with the minimum risk, was favored given the location and vascularity of the lesion. Occipitocervical fusion was recommended given ongoing bony destruction by the tumor and further expected iatrogenic instability upon resection. This was performed as a single stage given expected need for postoperative adjuvant radiation therapy and dynamic neck pain (Video 1). Surgical planning and decision making are detailed, including rationale and potential risks and benefits. We discuss positioning, equipment needs, and the importance of a multidisciplinary surgical team. Park bench positioning was used for part 1, left-sided extended far lateral and infratemporal fossa presigmoid approaches. For part 2, occipitocervical fusion, the patient was transitioned to prone position. The anatomy is highlighted in labeled pictures of the approach and dissection, and surgical video is presented for key surgical steps. Preoperative and postoperative imaging is analyzed. A desirable clinical outcome was obtained.