Pre-operative vs. post-operative stereotactic radiosurgery for operative metastatic brain tumors: study protocol for a phase III clinical trial.

BACKGROUND AND OBJECTIVES: Almost one third of cancer patients in the United States will develop brain metastases on an annual basis. Surgical resection is indicated in the setting of brain metastases for reasons, such as maximizing local control in select patients, decompression of mass effect, and/or tissue diagnosis. The current standard of care following resection of a brain metastasis has shifted from whole brain radiation therapy to post-operative stereotactic radiosurgery (SRS). However, there is a significant rate of local recurrence within one year of postoperative SRS. Emerging retrospective and prospective data suggest pre-operative SRS is a safe and potentially effective treatment paradigm for surgical brain metastases. This trial intends to determine, for patients with an indication for resection of a brain metastasis, whether there is an increase in the time to a composite endpoint of adverse outcomes; including the first occurrence of either: local recurrence, leptomeningeal disease, or symptomatic radiation brain necrosis - in patients who receive pre-operative SRS as compared to patients who receive post-operative SRS. METHODS: This randomized phase III clinical trial compares pre-operative with post-operative SRS for brain metastases. A dynamic random allocation procedure will allocate an equal number of patients to each arm: pre-operative SRS followed by surgery or surgery followed by post-operative SRS. EXPECTED OUTCOMES: If pre-operative SRS improves outcomes relative to post-operative SRS, this will establish pre-operative SRS as superior. If post-operative SRS proves superior to pre-operative SRS, it will remain a standard of care and halt the increasing utilization of pre-operative SRS. If there is no difference in pre- versus post-operative SRS, then pre-operative SRS may still be preferred, given patient convenience and the potential for a condensed timeline. DISCUSSION: Emerging retrospective and prospective data have demonstrated some benefits of pre-op SRS vs. post-op SRS. This study will show whether there is an increase in the time to the composite endpoint. Additionally, the study will compare overall survival; patient-reported outcomes; morbidity; completion of planned therapies; time to systemic therapy; time to regional progression; time to CNS progression; time to subsequent treatment; rate of radiation necrosis; rate of local recurrence; and rate of leptomeningeal disease. TRIAL REGISTRATION NUMBER: NCT03750227 (Registration date: 21/11/2018).

CSF dynamics in long-standing overt ventriculomegaly in adults.

OBJECTIVE: Long-standing overt ventriculomegaly in adults (LOVA) is a form of chronic hydrocephalus and its pathophysiology and treatment remain debated. An analysis of CSF dynamics in this condition has rarely been reported. The aim of this study was to analyze hydrodynamic characteristics of patients with suspected LOVA to discuss its pathophysiological mechanisms and the importance of CSF dynamics analysis for diagnosis and treatment of these patients. METHODS: This retrospective cohort study, conducted between May 2018 and October 2022, included adult patients aged > 18 years investigated in a department of neurosurgery through a lumbar infusion study for suspicion of LOVA (n = 23). These patients were then compared with a control cohort explored for suspicion of idiopathic normal pressure hydrocephalus (iNPH; n = 30). Clinical symptoms, radiological findings, and hydrodynamic parameters were analyzed. The authors specifically compared two hydrodynamic parameters: resistance to CSF outflow, or Rout, which relies on CSF resorption, and pressure-volume index (PVI), which reflect overall craniospinal compliance. The lumbar infusion study was considered pathological (confirming the diagnosis of chronic hydrocephalus) when at least one of these two parameters was altered. RESULTS: Rout was significantly less frequently increased (cutoff ≥ 12 mm Hg/ml/min) in patients with LOVA (52%) than in those with iNPH (97%; p < 0.001). In contrast, PVI was impaired (cutoff ≤ 25 ml) in both cohorts, i.e., in 61% of patients with LOVA and in 83% of patients with iNPH. Overall, the rate of pathological lumbar infusion study in LOVA (87%) was not statistically different than in iNPH (100%). However, PVI was the only impaired parameter most frequently found in those with LOVA (35%) compared with those with iNPH (3%; p = 0.002). CONCLUSIONS: This study suggests that there is a differential CSF dynamics pattern when comparing patients with LOVA versus those with iNPH. A higher proportion of patients with LOVA showed isolated compliance impairment. These findings highlight the utility of CSF dynamics analysis for the evaluation of patients with suspected chronic obstructive hydrocephalus such as LOVA. Future research with larger case series may help define diagnosis and treatment algorithms of chronic obstructive hydrocephalus based on CSF dynamics analysis, in addition to clinical and radiological criteria.

Objective assessment of patients with idiopathic normal pressure hydrocephalus following ventriculoperitoneal shunt placement using activity-monitoring data: pilot study.

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) results in significant morbidity in the elderly with symptoms of dementia, gait instability, and urinary incontinence. In well-selected patients, ventriculoperitoneal shunt (VPS) placement often results in clinical improvement. Most postshunt assessments of patients rely on subjective scales. The goal of this study was to assess the utility of remote activity monitoring to provide objective evidence of gait improvement following VPS placement for iNPH. METHODS: Patients with iNPH were prospectively enrolled and fitted with 5 activity monitors (on the hip and bilateral thighs and ankles) that they wore for 4 days preoperatively within 30 days of surgery and for 4 days within 30 days postoperatively. Monitors collected continuous data for number of steps, cadence, body position (upright, prone, supine, and lateral decubitus), gait entropy, and the proportion of each day spent active or static. Data were retrieved from the devices and a comparison of pre- and postoperative movement assessment was performed. The gait data were also correlated with formal clinical gait assessments before and after lumbar puncture and with motion analysis laboratory testing at baseline and 1 month and 1 year after VPS placement. RESULTS: Twenty patients fulfilled the inclusion and exclusion criteria (median age 76 years). The baseline median number of daily steps was 1929, the median percentage of the day spent inactive was 70%, the median percentage of the day with a static posture was 95%, the median gait velocity was 0.49 m/sec, and the median number of steps required to turn was 8. There was objective improvement in median entropy from pre- to postoperatively, increasing from 0.6 to 0.8 (p = 0.002). There were no statistically significant differences for any of the remaining variables measured by the activity monitors when comparing the preoperative to the 1-month postoperative time point. All variables from motion analysis testing showed statistically significant differences or a trend toward significance at 1 year after VPS placement. Among the significantly correlated variables at baseline, cadence was inversely correlated with percentage of gait cycle spent in the support phase (contact with ground vs swing phase). CONCLUSIONS: This pilot study suggests that activity monitoring provides an early objective measure of improvement in gait entropy after VPS placement among patients with iNPH, although a more significant improvement was noted on the detailed clinical gait assessments. Further long-term studies are needed to determine the utility of remote monitoring for assessing gait improvement following VPS placement.

Surgical clipping of a non-ruptured ophthalmic aneurysm through an extradural micropterional keyhole approach.

BACKGROUND: Clipping continues to be one of the treatment strategies for ophthalmic artery aneurysms not amenable for stenting or coiling, or when long-term treatment durability is a concern. However, crescent development of endovascular techniques demands minimal invasiveness in the transcranial approaches while ensuring satisfactory results. METHODS: We describe an extradural micropterional keyhole approach (eMKA) to the paraclinoid region and highlight the key anatomical elements of this surgical approach. CONCLUSION: The eMKA is a minimally invasive approach that provides access to the paraclinoid region using an extradural corridor. Therefore, it is suitable for clipping of ophthalmic artery aneurysms and other paraclinoid aneurysms.

Timing of surgical treatment for idiopathic normal pressure hydrocephalus: association between treatment delay and reduced short-term benefit.

OBJECTIVE A growing body of evidence suggests that longer durations of preoperative symptoms may correlate with worse postoperative outcomes following cerebrospinal fluid (CSF) diversion for treatment of idiopathic normal pressure hydrocephalus (iNPH). The aim of this study is to determine whether the duration of preoperative symptoms alters postoperative outcomes in patients treated for iNPH. METHODS The authors conducted a retrospective review of 393 cases of iNPH involving patients treated with ventriculoperitoneal (VP) shunting. The duration of symptoms prior to the operative intervention was recorded. The following outcome variables were assessed at baseline, 6 months postoperatively, and at last follow-up: gait performance, urinary continence, and cognition. RESULTS The patients' median age at shunt placement was 74 years. Increased symptom duration was significantly associated with worse gait outcomes (relative risk (RR) 1.055 per year of symptoms, p = 0.037), and an overall absence of improvement in any of the classic triad symptomology (RR 1.053 per year of symptoms, p = 0.033) at 6 months postoperatively. Additionally, there were trends toward significance for symptom duration increasing the risk of having no 6-month postoperative improvement in urinary incontinence (RR 1.049 per year of symptoms, p = 0.069) or cognitive symptoms (RR 1.051 per year of symptoms, p = 0.069). However, no statistically significant differences were noted in these outcomes at last follow-up (median 31 months). Age stratification by decade revealed that prolonging symptom duration was significantly associated with lower Mini-Mental Status Examination scores in patients aged 60-70 years, and lack of cognitive improvement in patients aged 70-80 years. CONCLUSIONS Patients with iNPH with longer duration of preoperative symptoms may not receive the same short-term benefits of surgical intervention as patients with shorter duration of preoperative symptoms. However, with longer follow-up, the patients generally reached the same end point. Therefore, when managing patients with iNPH, it may take longer to see the benefits of CSF shunting when patients present with a longer duration of preoperative symptoms.

Far-lateral transcondylar approach for microsurgical trapping of an anterior inferior cerebellar artery aneurysm.

Aneurysms of the posterior circulation remain challenging lesions given their proximity to the brainstem and cranial nerves. Many of these aneurysms may best be approached through a retrosigmoid-suboccipital craniectomy with a far-lateral transcondylar extension. In this narrated video illustration, we present the case of a 37-year-old man with an incidentally discovered right-sided anterior inferior cerebellar artery (AICA) aneurysm. Diagnostic studies included CT angiography and cerebral angiography. A suboccipital craniectomy and far-lateral transcondylar extension were performed for microsurgical trapping and excision of the AICA aneurysm. The techniques of the retrosigmoid craniectomy, C-1 laminectomy, condylectomy and microsurgical trapping of the aneurysm are reviewed. The video can be found here: http://youtu.be/JiM3CXVwXnk.

The butterfly effect on glioblastoma: is volumetric extent of resection more effective than biopsy for these tumors?

A subset of patients with glioblastoma (GBM) have butterfly GBM (bGBM) that involve both cerebral hemispheres by crossing the corpus callosum. The prognoses, as well as the effectiveness of surgery and adjuvant therapy, are unclear because studies are few and limited. The goals of this study were to: (1) determine if bGBM have worse outcomes than patients with non-bGBM, (2) determine if surgery is more effective than biopsy, and (3) identify factors independently associated with improved outcomes for these patients. Adult patients who underwent surgery for a newly diagnosed primary GBM at an academic tertiary-care institution between 2007 and 2012 were retrospectively reviewed and tumors were volumetrically measured. Of the 336 patients with newly diagnosed GBM who were operated on, 48 (14 %) presented with bGBM, where 29 (60 %) and 19 (40 %) underwent surgical resection and biopsy, respectively. In multivariate analysis, a bGBM was independently associated with poorer survival [HR (95 % CI) 1.848 (1.250-2.685), p < 0.003]. In matched-pair analysis, patients who underwent surgical resection had improved median survival than biopsy patients (7.0 vs. 3.5 months, p = 0.03). In multivariate analysis, increasing percent resection [HR (95 % CI) 0.987 (0.977-0.997), p = 0.01], radiation [HR (95 % CI) 0.431 (0.225-0.812), p = 0.009], and temozolomide [HR (95 % CI) 0.413 (0.212-0. 784), p = 0.007] were each independently associated with prolonged survival among patients with bGBM. This present study shows that while patients with bGBM have poorer prognoses compared to non-bGBM, these patients can also benefit from aggressive treatments including debulking surgery, maximal safe surgical resection, temozolomide chemotherapy, and radiation therapy.

Microsurgical obliteration of a thoracic spinal perimedullary arteriovenous fistula.

Spinal vascular lesions are rare and may be classified as a) dural arteriovenous fistulas (AVFs), b) arteriovenous malformations, or c) perimedullary AVFs. In this narrated video illustration, we present the case of a 71-year-old woman who presented with progressive bilateral lower extremity weakness and urinary retention who was diagnosed with a thoracic spinal perimedullary arteriovenous fistula. The diagnostic studies included a thoracic MRI and spinal angiogram. A multilevel thoracic laminoplasty was performed for microsurgical obliteration of the AVF. The techniques of intraoperative angiography, thoracic laminoplasty and microsurgical obliteration and resection of the AVF are reviewed. The video can be found here: http://youtu.be/5vVp3oq5sLg.

Hearing preservation outcomes using direct cranial nerve eight and auditory brainstem response neuromonitoring in the resection of vestibular schwannomas.

OBJECTIVE: Advancements in microsurgical technique and technology continue to improve outcomes in patients with skull base tumor. The primary cranial nerve eight monitoring systems used in hearing preservation surgery for vestibular schwannomas (VSs) are direct cranial nerve eight monitoring (DCNEM) and auditory brainstem response (ABR), although current guidelines are unable to definitively recommend one over the other due to limited literature on the topic. Thus, further research is needed to determine the utility of DCNEM and ABR. The authors performed a retrospective cohort study and created an interactive model that compares hearing preservation outcomes based on tumor size in patients receiving ABR+DCNEM and ABR-only monitoring. METHODS: Twenty-eight patients received ABR+DCNEM and 72 patients received ABR-only monitoring during VS hearing preservation surgery at a single tertiary academic medical center between January 2008 and November 2022. Inclusion criteria consisted of adult patients with a preoperative American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) hearing classification of A or B. Tumor size was measured as the maximal medial to lateral length, including the internal auditory canal component. RESULTS: Overall hearing preservation (word recognition score [WRS] > 0%) was achieved in 31 patients with ABR-only monitoring (43.1%) and in 18 patients with ABR+DCNEM (64.3%). Serviceable hearing preservation (AAO-HNS class A or B) was attained in 19 patients with ABR-only monitoring (26.4%) and in 11 patients with ABR+DCNEM (39.3%). There was no difference in overall hearing preservation between the two groups (p = 0.13). Change in tumor size was not associated with the odds of serviceable hearing preservation for the ABR-only group (p = 0.89); however, for ABR+DCNEM, there was some indication of an interaction between tumor size and the association of ABR+DCNEM versus ABR-only monitoring, with the odds of serviceable hearing preservation at p = 0.089. Furthermore, with ABR+DCNEM, every 0.5-cm increase in tumor size was associated with a decreased odds of serviceable hearing preservation on multivariable analysis (p = 0.05). For both overall and serviceable hearing preservation, a worse preoperative AAO-HNS classification was associated with a decreased odds of preservation (OR 0.43, 95% CI 0.19-0.97, p = 0.042; OR 0.17, 95% CI 0.053-0.55, p = 0.0031, respectively). CONCLUSIONS: The result of this interactive model study proposes that there may be a higher chance of hearing preservation when using ABR+DCNEM rather than ABR alone for smaller tumors, with that relationship reversing as tumor size increases.

The longitudinal risk of hemorrhage of melanoma brain metastases after Gamma Knife radiosurgery.

OBJECTIVE: The objective of this study was to analyze the hemorrhagic risk of melanoma brain metastases after Gamma Knife radiosurgery (GKRS). METHODS: A prospective institutional database was retrospectively queried to identify patients who underwent GKRS for melanoma brain metastases between 1990 and 2021. Lesional hemorrhage was defined as definite or possible based on radiologists' readings, and severity was graded according to Common Terminology Criteria for Adverse Events. RESULTS: Two hundred ninety-one patients with 1083 lesions treated in 419 sessions were identified. The mean (± SD) patient age was 60 ± 15 years, and 61% were male. The median follow-up period for overall survival (OS) was 11 (range 0-214) months with 581 patient-years. Definite/possible lesional hemorrhages occurred in 13% of lesions, with grade 3 hemorrhages observed in 4% of lesions. Surgical intervention was required in 2% of cases (5% of patients), and all resected lesions were pathologically consistent with melanoma. A decreased risk of definite/possible lesional hemorrhage was associated with a later time period between 2015 and 2021 (OR 0.45, 95% CI 0.266-0.75, p = 0.0021), increased marginal dose (OR 0.91, 95% CI 0.83-0.99, p = 0.037), antiplatelet use post-GKRS (OR 0.195, 95% CI 0.083-0.46, p < 0.001), and whole-brain radiotherapy (WBRT; OR 0.53, 95% CI 0.344-0.82, p = 0.0042). After 2015, more patients received anticoagulation, B-Raf proto-oncogene inhibitors, and immune checkpoint inhibitors, and fewer received bevacizumab (p < 0.001). The cumulative risk of lesional hemorrhage was 17%-20% at 36 months from GKRS, with 95%-96% of cases occurring within 12 months. The median patient OS was 11 (95% CI 9-13) months, and multivariate Cox regression analysis revealed that antiplatelet agents (hazard ratio [HR] 0.66, 95% CI 0.45-0.96, p = 0.031) and immune checkpoint inhibitors (HR 0.35, 95% CI 0.26-0.48, p < 0.001) were associated with longer OS, while WBRT (HR 1.36, 95% CI 1.02-1.81, p = 0.037) and definite/possible hemorrhage (HR 1.39, 95% CI 1.04-1.85, p = 0.024) were associated with shorter OS. CONCLUSIONS: The definite hemorrhage risk of melanoma brain metastases after GKRS was 17% in the first 3 years and 95% of the lesional hemorrhage occurred within the 1st year. Surgical intervention was needed in 5% of patients. Antiplatelet agents and immune checkpoint inhibitors were associated with improved OS, while definite/possible hemorrhage was associated with worse OS.

The dynamic impact of location and resection on the glioma CSF proteome.

While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples, including anatomical location and post-surgical changes, remains unknown. To that end, pre- versus post-resection intracranial CSF samples were obtained at early (1-16 days; n=20) or delayed (86-153 days; n=11) timepoints for patients with glioma. Paired lumbar-versus-intracranial glioma CSF samples were also obtained (n=14). Using aptamer-based proteomics, we identify significant differences in the CSF proteome between lumbar, subarachnoid, and ventricular CSF. Our analysis of serial intracranial CSF samples suggests the early potential for disease monitoring and evaluation of pharmacodynamic impact of targeted therapies. Importantly, we found that resection had a significant, evolving longitudinal impact on the CSF proteome. Proteomic data are provided with individual clinical annotations as a resource for the field. One Sentence Summary: Glioma cerebrospinal fluid (CSF) accessed intra-operatively and longitudinally via devices can reveal impacts of treatment and anatomical location.

Effect of Extent of Resection on Survival of Patients with Glioblastoma, IDH-Wild-Type, WHO Grade 4 (WHO 2021): Systematic Review and Meta-Analysis.

BACKGROUND: In light of the recently updated World Health Organization (WHO) 2021 central nervous system tumor classifications, the aim of the present study was to establish the effect of the resection extent on overall survival (OS) and progression-free survival (PFS) for patients who met the current diagnostic criteria for glioblastoma, isocitrate dehydrogenase (IDH)-wild-type (WT), WHO grade 4. METHODS: A systematic literature search was performed using the following databases: PubMed, Web of Science, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews and ClinicalTrials.gov to identify studies that had compared OS and PFS after gross total resection (GTR) versus subtotal resection (STR) or biopsy for glioblastoma IDH-WT. RESULTS: We identified 1439 studies, of which 9 met the inclusion and/or exclusion criteria. Of the 2023 patients, 788 had undergone GTR. The meta-analysis showed a significant increase in the OS and PFS duration after GTR for glioblastoma IDH-WT, with a median OS of 20 months (95% confidence interval [CI], 17-25) after GTR versus 12 months (95% CI, 9-15) after STR (P < 0.0001). The median PFS was 11 months (95% CI, 9-12) after GTR versus 7 months (95% CI, 5-7) after STR (P < 0.0001). GTR was associated with a 51% reduction in the mortality risk (hazard ratio, 0.49; 95% CI, 0.36-0.65) and a 42% reduction in the progression risk (hazard ratio, 0.58; 95% CI, 0.39-0.88) compared with STR. CONCLUSIONS: The results from our systematic review suggest that GTR is associated with improved OS and PFS compared with STR for glioblastoma, IDH-WT, WHO grade 4 (WHO 2021). However, our findings were limited by the various study designs and significant clinical and methodologic heterogeneity among the studies.

INPH and parkinsonism: A positive shunt response with a negative tap test.

Introduction: The aim of this study was to compare clinical and functional performances of idiopathic normal pressure hydrocephalus (INPH) patients with and without parkinsonism at the initial evaluation, 72 h after the cerebrospinal fluid tap test (CSF TT), and 6 months after ventriculoperitoneal shunt (VPS) surgery. Materials and methods: This is an observational prospective study on patients with INPH who underwent VPS. Patients were classified into INPH with parkinsonism (INPH-P+) and without parkinsonism (INPH-P-). We used the time up and go (TUG) test, Tinetti Performance-Oriented Mobility Assessment (POMA) test, INPH grading scale (INHPGS), and modified Rankin scale (mRS) at baseline, 72 h after CSF TT, and 6 months after VPS surgery. Results: A total of 64 patients with probable INPH were included, 12 patients with INPH-P+ and 52 controls with INPH-P-. Patients with INPH showed significant improvement in all clinical and neurological parameters after VPS including TUG, Tinetti POMA, INPHGS, and mRS (p < 0.001) with the exception of mRS where there was no significant change 72 h after CSF TT compared to baseline for patients with INPH (p = 0.182). Patients with INPH-P+ performed significantly worse than patients with INPH-P- on Tinetti POMA and mRS at baseline, at 72 h post-CSF TT, and at 6 months post-VPS with INPHGS being worst at 72 h post-CSF TT. There was no difference between patients with INPH-P+ and patients with INPH-P- for TUG at baseline (p = 0.270), at 72 h post-CSF TT (p = 0.487), and at 6 months post-VPS (p = 0.182). Patients with INPH-P+ did not show any change in any of the parameters at 72 h post-CSF TT compared to baseline; however, there was a trend toward improvement on TUG (p = 0.058), Tinetti gait (p = 0.062), and Tinetti total (p = 0.067). INPH-P+ significantly improved in all parameters 6 months post-VPS compared to baseline except for mRS (p = 0.124). Patients with INPH-P- significantly improved in all parameters at 72 h post-CSF TT and at 6 months post-VPS compared to baseline, respectively, except on mRS 72 h after CSF TT (p = 0.299). Conclusion: Patients with INPH and parkinsonism overall do worse than patients without parkinsonism. An unsatisfying response to the CSF tap test in INPH patients with parkinsonism should not be used as an exclusion criterion from VPS surgery since patients with and without parkinsonism showed significant improvement post-VPS.

MGMT Methylated High Grade Glioma with Distant Recurrence and Stable Original Tumor Site: Case Series.

We present three cases of O6-Methylguanine-DNA Methyl-transferase (MGMT) methylated high grade gliomas with distant recurrence. All three patients had a radiographic stability of original tumor site at time of distant recurrence indicating impressive local control with Stupp protocol in patients with a MGMT methylated tumors. All patients had a poor outcome after distant recurrence. For one patient Next Generation Sequencing (NGS) was available for both original and recurrent tumor and did not reveal any difference other than high tumor mutational burden in the distant recurrent tumor. Understanding risk factors of distant recurrence in MGMT methylated tumors and investigating correlations between recurrences will help plan therapeutic strategies to prevent distant recurrence and improve survival of these patients.

Effect of Stent Porosity, Platelet Function Test Usage, and Dual Antiplatelet Therapy Duration on Clinical and Radiographic Outcomes After Stenting for Cerebral Aneurysms: A Meta-Analysis.

BACKGROUND: The use of stents with various porosities for treating cerebral aneurysms requires dual antiplatelet therapy (DAPT) without clear guidelines on the utility of platelet function tests (PFTs) and the duration of DAPT. We sought to determine the effects of stent porosity, PFT usage, and DAPT duration on the radiographic and clinical outcomes after stenting of cerebral aneurysms. METHODS: PubMed was searched on March 29, 2021 for studies of cerebral aneurysm stenting that had specified the stent type and DAPT duration. A random effects meta-analysis was used to measure the prevalence of nonprocedural thrombotic and hemorrhagic events, clinical outcomes, aneurysm occlusion, and in-stent stenosis stratified by stent porosity, PFT usage, and DAPT duration. RESULTS: The review yielded 105 studies (89 retrospective and 16 prospective) with 117 stenting cohorts (50 high porosity, 17 intermediate porosity, and 50 low porosity). In the high-, intermediate-, and low-porosity stenting cohorts, PFT usage was 26.0%, 47.1%, and 62.0% and the mean DAPT duration was 3.51 ± 2.33, 3.97 ± 1.92, and 5.18 ± 2.27 months, respectively. The intermediate-porosity stents showed a reduced incidence of hemorrhagic events (π = 0.32%) compared with low-porosity stents (π = 1.36%; P = 0.01) and improved aneurysm occlusion (π = 6.18%) compared with high-porosity stents (π = 14.42%; P = 0.001) and low-porosity stents (π = 11.71%; P = 0.04). The prevalence of in-stent stenosis was lower for the intermediate-porosity (π = 0.57%) and high-porosity (π = 1.51%) stents than for the low-porosity stents (π = 3.30%; P < 0.05). PFT use had resulted in fewer poor clinical outcomes (π = 3.54%) compared with those without PFT use (π = 5.94%; P = 0.04). The DAPT duration had no effect on the outcomes. CONCLUSIONS: In the present meta-analysis, which had selected for studies of cerebral aneurysm stenting that had reported the DAPT duration, intermediate-porosity stents and PFT use had resulted significantly improved outcomes. No effect of DAPT duration could be detected.

Methodological and analytical considerations for intra-operative microdialysis.

BACKGROUND: Microdialysis is a technique that can be utilized to sample the interstitial fluid of the central nervous system (CNS), including in primary malignant brain tumors known as gliomas. Gliomas are mainly accessible at the time of surgery, but have rarely been analyzed via interstitial fluid collected via microdialysis. To that end, we obtained an investigational device exemption for high molecular weight catheters (HMW, 100 kDa) and a variable flow rate pump to perform microdialysis at flow rates amenable to an intra-operative setting. We herein report on the lessons and insights obtained during our intra-operative HMW microdialysis trial, both in regard to methodological and analytical considerations. METHODS: Intra-operative HMW microdialysis was performed during 15 clinically indicated glioma resections in fourteen patients, across three radiographically diverse regions in each patient. Microdialysates were analyzed via targeted and untargeted metabolomics via ultra-performance liquid chromatography tandem mass spectrometry. RESULTS: Use of albumin and lactate-containing perfusates impacted subsets of metabolites evaluated via global metabolomics. Additionally, focal delivery of lactate via a lactate-containing perfusate, induced local metabolic changes, suggesting the potential for intra-operative pharmacodynamic studies via reverse microdialysis of candidate drugs. Multiple peri-operatively administered drugs, including levetiracetam, cefazolin, caffeine, mannitol and acetaminophen, could be detected from one microdialysate aliquot representing 10 min worth of intra-operative sampling. Moreover, clinical, radiographic, and methodological considerations for performing intra-operative microdialysis are discussed. CONCLUSIONS: Intra-operative HMW microdialysis can feasibly be utilized to sample the live human CNS microenvironment, including both metabolites and drugs, within one surgery. Certain variables, such as perfusate type, must be considered during and after analysis. Trial registration NCT04047264.

Blood-brain barrier disruption defines the extracellular metabolome of live human high-grade gliomas.

The extracellular microenvironment modulates glioma behaviour. It remains unknown if blood-brain barrier disruption merely reflects or functionally supports glioma aggressiveness. We utilised intra-operative microdialysis to sample the extracellular metabolome of radiographically diverse regions of gliomas and evaluated the global extracellular metabolome via ultra-performance liquid chromatography tandem mass spectrometry. Among 162 named metabolites, guanidinoacetate (GAA) was 126.32x higher in enhancing tumour than in adjacent brain. 48 additional metabolites were 2.05-10.18x more abundant in enhancing tumour than brain. With exception of GAA, and 2-hydroxyglutarate in IDH-mutant gliomas, differences between non-enhancing tumour and brain microdialysate were modest and less consistent. The enhancing, but not the non-enhancing glioma metabolome, was significantly enriched for plasma-associated metabolites largely comprising amino acids and carnitines. Our findings suggest that metabolite diffusion through a disrupted blood-brain barrier may largely define the enhancing extracellular glioma metabolome. Future studies will determine how the altered extracellular metabolome impacts glioma behaviour.

Myo1e overexpression in lung adenocarcinoma is associated with increased risk of mortality.

This study aims to perform a comprehensive genomic analysis to assess the influence of overexpression of MYO1E in non-small cell lung carcinoma (NSCLC) and whether there are differences in survival and mortality risk in NSCLC patients depending on both DNA methylation and RNA expression of MYO1E. The DNA methylation probe cg13887966 was inversely correlated with MYO1E RNA expression in both LUAD and LUSC subpopulations showing that lower MYO1E RNA expression was associated with higher MYO1E DNA methylation. Late stages of lung cancer showed significantly lower MYO1E DNA methylation and significantly higher MYO1E RNA expression for LUAD but not for LUSC. Low DNA methylation as well as high RNA expression of MYO1E are associated with a shorter median survival time and an increased risk of mortality for LUAD, but not for LUSC. This study suggests that changes in MYO1E methylation and expression in LUAD patients may have an essential role in lung cancer's pathogenesis. It shows the utility of MYO1E DNA methylation and RNA expression in predicting survival for LUAD patients. Also, given the low normal expression of MYO1E in blood cells MYO1E DNA methylation has the potential to be used as circulating tumor marker in liquid biopsies.

[Atypical choroid plexus papilloma in adults: case report and literature review]. / Papiloma atípico de los plexos coroideos en el adulto: publicación de un caso clínico y revisión de la bibliografía.

INTRODUCTION: Atypical choroid plexus papilloma is a rare tumour, recently defined by the World Health Organisation and with very few cases reported to date. Choroid plexus tumours are rare intraventricular neoplasms originating from choroid plexus epithelium, with benign papillomas being more frequent than carcinomas. Most of these lesions appear in children, mainly located in the lateral ventricles. Those arising from the fourth ventricle are more frequent in adulthood. Surgery with complete resection can be curative in papillomas, with 5-year survival rates close to 100% and occasional recurrences. Radical surgery in carcinomas is difficult and usually requires adjuvant therapy, prognosis is worse and survival rates are lower. We report a case of atypical choroid plexus papilloma in adulthood located in the fourth ventricle, describing the different therapeutic options and reviewing the existing literature. CASE REPORT: 38-year old male with an atypical choroid plexus papilloma located in the fourth ventricle, totally resected by posterior fossa craniectomy and telovellar approach. CONCLUSION: Atypical choroid plexus papillomas are associated with an increased risk of recurrence or malignant transformation when compared to "typical" papillomas. At present, complete surgical excision and close follow-up seems to be the most reliable treatment. Adjuvant chemotherapy or radiotherapy should be considered in cases of partial resection, recurrence or dissemination.

Treatment of tegmen dehiscence using a middle fossa approach and autologous temporalis fascia graft: Outcomes from a single center.

INTRODUCTION: Although bony defects of the tegmen surface are relatively common, the majority of dehiscences are asymptomatic. For those who experience symptoms, there is a wide spectrum of relatively benign manifestations such as hearing loss and otorrhea to potentially more serious but rare sequelae such as epilepsy and meningitis. Surgical management of tegmen dehiscences (TDs) can help prevent these symptoms. In this manuscript, we present one of the largest reported single team experiences of using a temporal craniotomy with middle cranial fossa approach and temporalis fascia graft in the treatment of tegmen defects. METHODS: We retrospectively reviewed every case of a TD surgically repaired by the same neurosurgeon/otolaryngologist team at Loyola University Medical Center from May 2015 to January 2022. In our chart review, we identified 44 patients with 48 cases of tegmen defect repair. We analyzed patient characteristics, operative details, and postoperative outcomes. RESULTS: 44 patients met inclusion criteria for the presence of TD (mean age 55 years, 55% male, and average body mass index 35.6). 89% of these patients had no clear etiology for the dehiscence. Commonly reported symptoms were hearing loss (89%) and CSF otorrhea (82%). The least reported presenting signs and symptoms were seizures (5%) and meningitis (2%). Most defects were repaired with both temporalis fascial and calvarial bone grafts (63%), while a minority were treated with temporalis fascia only (33%), temporalis fascia with muscle (2%), or fascia lata (2%). Every patient in our sample experienced resolution of CSF otorrhea after tegmen repair and 81% of the sample reported subjective hearing improvements after surgery. 6% of our sample had post-operative infections and 8% of patients underwent repeat unilateral surgery for a surgical complication. CONCLUSION: Craniotomy for middle fossa approach using autologous temporalis fascial grafts is a safe and effective method for the treatment of TD. These procedures should be performed by experienced and multidisciplinary teams.