Results from a first-in-human phase I safety trial to evaluate the use of a vascularized pericranial/temporoparietal fascial flap to line the resection cavity following resection of newly diagnosed glioblastoma.

PURPOSE: The efficacy of systemic therapies for glioblastoma (GBM) remains limited due to the constraints of systemic toxicity and blood-brain barrier (BBB) permeability. Temporoparietal fascial flaps (TPFFs) and vascularized peri cranial flaps (PCF) are not restricted by the blood-brain barrier (BBB), as they derive their vascular supply from branches of the external carotid artery. Transposition of a vascularized TPFF or PCF along a GBM resection cavity may bring autologous tissue not restricted by the BBB in close vicinity to the tumor bed microenvironment, permit ingrowth of vascular channels fed by the external circulation, and offer a mechanism of bypassing the BBB. In addition, circulating immune cells in the vascularized flap may have better access to tumor-associated antigens (TAA) within the tumor microenvironment. We conducted a first-in-human Phase I trial assessing the safety of lining the resection cavity with autologous TPFF/PCF of newly diagnosed patients with GBM. METHODS: 12 patients underwent safe, maximal surgical resection of newly diagnosed GBMs, followed by lining of the resection cavity with a pedicled, autologous TPFF or PCF. Safety was assessed by monitoring adverse events. Secondary analysis of efficacy was examined as the proportion of patients experiencing progression-free disease (PFS) as indicated by response assessment in neuro-oncology (RANO) criteria and overall survival (OS). The study was powered to determine whether a Phase II study was warranted based on these early results. For this analysis, subjects who were alive and had not progressed as of the date of the last follow-up were considered censored and all living patients who were alive as of the date of last follow-up were considered censored for overall survival. For simplicity, we assumed that a 70% PFS rate at 6 months would be considered an encouraging response and would make an argument for further investigation of the procedure. RESULTS: Median age of included patients was 57 years (range 46-69 years). All patients were Isocitrate dehydrogenase (IDH) wildtype. Average tumor volume was 56.6 cm3 (range 14-145 cm3). Resection was qualified as gross total resection (GTR) of all of the enhancing diseases in all patients. Grade III or above adverse events were encountered in 3 patients. No Grade IV or V serious adverse events occurred in the immediate post-operative period including seizure, infection, stroke, or tumor growing along the flap. Disease progression at the site of the original tumor was identified in only 4 (33%) patients (median 23 months, range 8-25 months), 3 of whom underwent re-operation. Histopathological analyses of those implanted flaps and tumor bed biopsy at repeat surgery demonstrated robust immune infiltrates within the transplanted flap. Importantly, no patient demonstrated evidence of tumor infiltration into the implanted flap. At the time of this manuscript preparation, only 4/12 (33%) of patients have died. Based on the statistical considerations above and including all 12 patients 10/12 (83.3%) had 6-month PFS. The median PFS was 9.10 months, and the OS was 17.6 months. 4/12 (33%) of patients have been alive for more than two years and our longest surviving patient currently is alive at 60 months. CONCLUSIONS: This pilot study suggests that insertion of pedicled autologous TPFF/PCF along a GBM resection cavity is safe and feasible. Based on the encouraging response rate in 6-month PFS and OS, larger phase II studies are warranted to assess and reproduce safety, feasibility, and efficacy. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION FOR PROSPECTIVELY REGISTERED TRIALS: ClinicalTrials.gov ID NCT03630289, dated: 08/02/2018.

Dual Layer vs Single Layer Woven EndoBridge Device in the Treatment of Intracranial Aneurysms: A Propensity Score-Matched Analysis.

BACKGROUND: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms. METHODS: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture. RESULTS: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23). CONCLUSION: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.

The Impact of Dual Antiplatelet Therapy Duration on Unruptured Aneurysm Occlusion After Flow Diversion: A Multicenter Study.

OBJECTIVE: Endoluminal flow diversion reduces blood flow into intracranial aneurysms, promoting thrombosis. Postprocedural dual antiplatelet therapy (DAPT) is necessary for the prevention of thromboembolic complications. The purpose of this study is to therefore assess the impact that the type and duration of DAPT has on aneurysm occlusion rates and iatrogenic complications after flow diversion. METHODS: A retrospective review of a multicenter aneurysm database was performed from 2012 to 2020 to identify unruptured intracranial aneurysms treated with single device flow diversion and ≥12-month follow-up. Clinical and radiologic data were analyzed with aneurysm occlusion as a function of DAPT duration serving as a primary outcome measure. RESULTS: Two hundred five patients underwent flow diversion with a single pipeline embolization device with 12.7% of treated aneurysms remaining nonoccluded during the study period. There were no significant differences in aneurysm morphology or type of DAPT used between occluded and nonoccluded groups. Nonoccluded aneurysms received a longer mean duration of DAPT (9.4 vs 7.1 months, P = 0.016) with a significant effect of DAPT duration on the observed aneurysm occlusion rate (F(2, 202) = 4.2, P = 0.016). There was no significant difference in the rate of complications, including delayed ischemic strokes, observed between patients receiving short (≤6 months) and prolonged duration (>6 months) DAPT (7.9% vs 9.3%, P = 0.76). CONCLUSIONS: After flow diversion, an abbreviated duration of DAPT lasting 6 months may be most appropriate before transitioning to low-dose aspirin monotherapy to promote timely aneurysm occlusion while minimizing thromboembolic complications.

FRED Jr stent for acute flow diversion in ruptured cerebral aneurysms arising from small-caliber vessels: a clinical case series.

OBJECTIVE: Treatment of ruptured aneurysms arising from small-caliber (< 2.5 mm) or distal vessels beyond the circle of Willis is considered challenging with all treatment modalities. Recently, the Flow Re-Direction Endoluminal Device Junior (FRED Jr) stent, designed for flow diversion in small arteries, was approved in the United States for the treatment of nonruptured aneurysms. Here, the authors report their experience using this device in the setting of subarachnoid hemorrhage (SAH). METHODS: Clinical and radiological records of patients sustaining SAH treated with a FRED Jr stent between June 2020 and October 2022 were reviewed. Treatment course, including antiplatelet therapy, external ventricular drain (EVD) management, and vasospasm, and clinical outcomes were analyzed. Angiographic results were assessed according to the O'Kelly-Marotta (OKM) grading scale. RESULTS: Nine patients at a median age of 62 (range 27-75) years were included. The median Hunt and Hess grade was II (IQR I) and the median modified Fisher grade was 4 (IQR 1). Aneurysm morphology types included saccular (6 patients), blister (1 patient), and dissecting (2 patients), and the aneurysms were located at the anterior communicating artery complex (n = 3) at the A2/A3 (n = 3), M2/M3 (n = 1), V4 (n = 1), and P2 (n = 1) arterial segments. All stents were deployed successfully with no intraprocedural complications. Postoperatively, no rebleeding events were encountered. Vasospasm therapy was initiated in 6 patients, and no symptomatic EVD-related hematomas were observed. Postoperative ischemic events were encountered in 2 patients. The median 3-month modified Rankin Scale score was 2 (IQR 1) for the 7 surviving patients, and 3-month radiographic follow-up revealed OKM grade D in 4 of 7 patients. CONCLUSIONS: Flow diversion using the FRED Jr stent is feasible as a potential treatment strategy for acutely ruptured aneurysms arising from small-caliber vessels. The complication profile reported in this series is comparable to those of historical microsurgical cohorts, and effective protection was conferred by this treatment modality. Therefore, our small cohort provides a glimpse into a new tool for successfully achieving acute flow diversion for this subset of difficult-to-treat aneurysms.

[FALSE POSITIVE 5-ALA INDUCED FLUORESCENCE OF HEMATOLOGICAL MALIGNANCIES, BENIGN TUMORS, INFECTIOUS AND INFLAMMATORY PATHOLOGIES PRESENTED AS BRAIN LESIONS - A CASE SERIES].

INTRODUCTION: The 5-aminolevulinic acid (5-ALA) fluorescence-guided resection is an essential part of the current state-of-the-art treatment of primary malignant brain tumors. Metabolized by tumor cells, creating Protoporphyrin-IX, which is fluorescent under UV light emitted from the microscope, 5-ALA facilitates visual distinction between the tumor and the normal brain tissue surrounding it, coloring it pink. This real-time diagnostic feature was shown to lead to more complete removal of the tumor and confers a survival benefit. Nevertheless, despite the high sensitivity and specificity that was described using this method, there are other pathological processes in which 5-ALA is being metabolized that fluoresce similarly to a malignant glial tumor.

Intraoperative neuromonitoring during resection of cranial meningiomas and its effect on the surgical workflow.

PURPOSE: Resection of meningiomas adjacent to the central sulcus entails a high rate of morbidity. Explored for intra-axial lesion resection, intraoperative neuromonitoring intraoperative neuromonitoring (IONM) has been shown to decrease neurological deficits. The use of IONM is relatively uncommon and is not considered routine practice in the removal of extra-axial lesions. We sought to characterize IONM's impact on the surgical workflow in supratentorial meningiomas. METHODS: We retrospectively analyzed a prospectively collected database, searching cases in which IONM was used for resection of meningioma between 2017 and 2020. We classified the IONM effect on surgical workflow into 5 distinct categories of workflow changes (WFC). RESULTS: Forty cases of meningiomas with IONM use were identified. In 1 case (class 1 WFC), the operation was stopped due to IONM input. In 5 cases (class 2 WFC), the tumor was incompletely resected due to input from the IONM. In 14 cases (35%), IONM leads to an alteration of the resection process (alteration of approach, class 3 WFC). In 4 cases (10%), anesthesia care was modified based on IONM input (class 4 WFC). In 16 cases, no changes were made (class 5 WFC). In all patients in whom a change was made (24 cases, WFC 1-4), only 8.3% suffered a temporary deficit, and there were no permanent deficits, whereas when no change was made, there were 18.75% temporary deficit and 6.25% permanent deficit. CONCLUSION: IONM has an impact during resection of meningiomas in eloquent areas and may guide the surgical technique, approach to tumor resection, and extent of resection.

Cranial transposition and revascularization of autologous omentum: a novel surgical technique for resection of recurrent glioblastoma multiforme.

Glioblastoma multiforme (GBM) patients continue to suffer a poor prognosis. The blood brain barrier (BBB) comprises one of the obstacles for therapy, creating a barrier that decreases the bioavailability of chemotherapeutic agents in the central nervous system. Previously, a vascularized temporoparietal fascial scalp flap (TPFF) lining the resection cavity was introduced in a trial conducted in our institution, in newly-diagnosed GBM patients in an attempt to bypass the BBB after initial resection. In this paper, we report on a new technique to bypass the BBB after re-resection and potentially to allow tumor antigens to be surveilled by the immune system. The study aims to assess the feasibility of performing a cranial transposition and revascularization of autologous omentum after re-resection of GBM. Laparoscopically harvested omental free flap was transposed to the resection cavity by a team consisting of neurosurgeons, otolaryngologists, and general surgeons. This was done as part of a single center, single arm, open-label, phase I study. Autologous abdominal omental tissue was harvested laparoscopically on its vascularized pedicle in 2 patients, transposed as a free flap, revascularized using external carotid artery, and carefully laid into the tumor resection cavity. Patients did well postoperatively returning to baseline activities. Graft viability was confirmed by cerebral angiogram. Omental cranial transposition of a laparoscopically harvested, vascularized flap, into the cavity of re-resected GBM patients is feasible and safe in the short term. Further studies are needed to ascertain whether such technique can improve progression free survival and overall survival in these patients.

Temporary vessel occlusion in cerebral aneurysm surgery guided by direct cortical motor evoked potentials.

BACKGROUND: Temporary clipping is an important tool in the vascular neurosurgeon's armamentarium. We routinely utilize intraoperative neurophysiological monitoring (IONM) for complex brain aneurysm surgery cases, relying on direct cortical motor evoked potential (DCMEP) alerts to guide the duration of temporary clipping. Previous studies have argued for relatively short and intermittent temporary clipping strategies. In this study, we sought to assess the maximal permissive temporary clipping time during complex aneurysm surgery. To do this, we assessed patient outcome in relation to temporary clip duration guided by DCMEP. METHODS: We queried our prospectively collected neuromonitoring database for anterior circulation aneurysm cases where temporary clipping was utilized by a single cerebrovascular surgeon between 2018 and 2021. Operative and IONM reports were reviewed. Patients in whom the duration of temporary clipping could not be determined were excluded. The operative strategy permissively allowed continuous temporary clipping as long as no neuromonitoring alerts were encountered. Maximal permissive parent artery occlusion time (Clipmax) was recorded as the longest duration of tolerated temporary vessel clipping without decrement in DCMEP. RESULTS: A total of 41 complex anterior circulation aneurysm clipping cases met criteria for this study. The mean Clipmax for all cases was just over 19 min and did not differ between ruptured and unruptured aneurysms. Initial alert times were not found to be predictive of final permissive temporary clip duration after re-perfusion. In 100% (41/41) of cases, the aneurysm was completely clip occluded without residual on catheter angiogram. Stable or improved modified Rankin Score was achieved in 98% (40/41) of cases at 3-month follow-up. CONCLUSIONS: This study demonstrates that using DCMEP can facilitate relatively long but safe temporary clipping durations in complex anterior circulation aneurysm surgery. In the endovascular era with only a limited subset of technically challenging aneurysms needing open surgical treatment, extended permissive temporary clipping guided by DCMEPs can significantly enhance a surgeon's ability to achieve excellent technical and clinical outcomes.

Intracranial Pulsating Balloon-Based Cardiac-Gated ICP Modulation Impact on Brain Oxygenation: A Proof-of-Concept Study in a Swine Model.

BACKGROUND: Brain oxygenation improvement is a sought-after goal in neurocritical care patients. Previously, we have shown that cerebral blood flow improvement by cardiac-gated intracranial pressure (ICP) modulation using an intracranial pulsating balloon is feasible in a swine model. We sought to explore specific ICP modulation protocols to assess the feasibility of influencing brain oxygenation. METHODS: A previously presented electrocardiogram (ECG)-gated intracranial balloon pump in which volume, timing, and duty cycle of balloon inflation could be altered was used. Different protocols were tested in a swine model of normal and elevated ICP attained by intracranial fluid infusion with continuous monitoring of physiological parameters, and brain tissue oxygen tension (PbtO2) was measured at baseline and after device activation. RESULTS: We studied five swine, subjected to two main protocols differing in their phase relative to the cardiac cycle. In reduced brain perfusion status (ICP > 20 mm Hg, PbtO2 < 15 mm Hg), the late-diastolic-early-systolic (Inflation/deflation) protocol showed consistent elevation in PbtO2 (+ 9%, p < 0.01), coupled with ICP reduction (- 12%, p < 0.01), whereas the early-systolic-late-diastolic (inflation/deflation) protocol resulted in PbtO2 reduction (- 4%, p < 0.01), coupled with ICP increase (+ 5% above baseline, p < 0.01). No significant changes in brain oxygenation or ICP were observed at normal perfusion status (ICP < 20 mm Hg, PbtO2 > 15 mm Hg). CONCLUSIONS: Intracranial cardiac-gated balloon pump activation can influence cerebral oxygenation and raise PbtO2 above threshold values. This study supports the concept of late-diastolic pressure rise, coupled with early-systolic pressure drop, as a potential effector of flow augmentation leading to improve brain tissue oxygenation. Further studies are warranted to assess the translational potential of using an intracranial cardiac-gated balloon pump device to improve brain tissue oxygenation.

Improved Pressure Equalization Ratio Following Mannitol Administration in Patients With Severe TBI: A Preliminary Study of a Potential Bedside Marker for Response to Therapy.

BACKGROUND: Performing a cerebrospinal fluid (CSF) drainage challenge can be used to measure the pressure equalization (PE) ratio, which describes the extent to which CSF drainage can equalize pressure to the height of the external ventricular drain and may serve as a correlate of cerebral edema. We sought to assess whether treatment with mannitol improves PE ratio in patients with severe traumatic brain injury (TBI) with elevated intracranial pressure (ICP). METHODS: We studied consecutive patients with TBI and brain edema on computed tomography scan and an external ventricular drain (EVD), admitted to the neurointensive care unit. PE ratio, defined as ICP prior to CSF drainage minus ICP after CSF drainage divided by ICP prior to CSF drainage minus EVD height, was measured as previously described. Patients were treated with mannitol for raised ICP based on clinical indication and PE ratio measured before and after mannitol administration. RESULTS: We studied 20 patients with severe TBI with raised ICP. Mean ICP prior to mannitol treatment was 29 ± 7 mm Hg. PE ratio rose substantially after mannitol treatment (0.62 ± 0.24 vs. 0.29 ± 0.20, p < 0.0001), indicating an improved ability to drain CSF and equalize ICP with the preset height of the EVD. The combination of mannitol and CSF drainage led to an improved reduction in ICP compared with that seen before mannitol therapy (11 ± 2 mm Hg vs. 6 ± 2 mm Hg, p < 0.01), and led to a decrease in ICP below the 20 mm Hg threshold in 77% of cases. CONCLUSIONS: Treatment with mannitol leads to a substantial improvement in PE ratio that reflects the ability to achieve a greater decrease in ICP when CSF drainage is performed after mannitol administration. This preliminary study raises the possibility that PE ratio may be useful to follow response to therapy in patients with cerebral edema and raised ICP. Further studies to determine whether PE ratio may serve as an easily obtained and clinically useful surrogate marker for the extent of brain edema are warranted.

Technical aspects and operative nuances using a high-definition 4K-3-dimensional exoscope for carotid endarterectomy surgery.

PURPOSE: Carotid endarterectomy (CEA) is effective in treating carotid artery stenosis to prevent stroke. Historically, this operation has been performed utilizing loupe magnification with or without the operating microscope (OM). However, there remains a need for continued improvement in operative visualization and surgical ergonomics. Recently, newly developed digital 'exoscope' has provided the surgeon with unique lighting and magnification as well as improvements in surgical ergonomics and working angle. We sought to review our cumulative experience using a novel 4K high-definition (4K-HD) 3-dimensional (3D) exoscope (EX) for CEA surgery. METHODS: All CEA surgery cases at our institution between 2013 and 2019 using the 4K-HD 3D EX were reviewed. Operative parameters, patient outcome and operator's assessment of the EX compared to OM-assisted cases was conducted. RESULTS: 28 patients were treated, 10 of which were operated using the EX. All procedures were performed without perioperative complications, or significant differences in operative parameters (blood loss <20 cm3 and 164 ± 49.5 minutes) compared to OM-assisted cases. Operators reported improved level of comfort performing 'high' bifurcation surgery and improved visualization and posture during inspection of the distal ICA lumen as primary advantages of EX-assisted CEA over OM-assisted CEA. CONCLUSIONS: The ORBEYE EX, albeit a learning curve necessitating a short period of the OR team, provided safety and outcome comparable to OM-assisted surgery. Potential advantages noted were improved visualization and ergonomics specifically for when extreme working angles were required. Our experience suggests that the exoscope may become a valuable alternative to standard magnification tools in CEA surgery.

Characterizing the Response to Cerebrospinal Fluid Drainage in Patients with an External Ventricular Drain: The Pressure Equalization Ratio.

BACKGROUND: An external ventricular drain (EVD) is the gold standard for measurement of intracranial pressure (ICP) and allows for drainage of cerebrospinal fluid (CSF). Different causes of elevated ICP, such as CSF outflow obstruction or cerebral swelling, respond differently to CSF drainage. This is a widely recognized but seldom quantified distinction. We sought to define an index to characterize the response to CSF drainage in neurocritical care patients. METHODS: We studied consecutive patients admitted to the neurointensive care unit who had an EVD. The EVD was closed for 30 min prior to assessment. We documented pre-drainage ICP, opened EVD to drainage allowing CSF to drain until it ceased, and recorded post-drainage ICP at EVD closure. We calculated the pressure equalization (PE) ratio as the difference between pre-drainage ICP and post-drainage ICP divided by the difference between pre-drainage ICP and EVD height. RESULTS: We studied 60 patients (36 traumatic brain injury [TBI], 24 non-TBI). As expected, TBI patients had more signs of cerebral swelling on CT and smaller ventricles. Although TBI patients had significantly higher pre-drainage ICP (26 ± 10 mm Hg) than non-TBI patients (19 ± 5 mm Hg, p < 0.001) they drained less CSF (7 cc vs. 4 cc, p < 0.01). PE ratio was substantially higher in non-TBI than in TBI patients (0.86 ± 0.36 vs. 0.43 ± 0.31, p < 0.0001), indicating that non-TBI patients were better able to equalize pressure with EVD height than TBI patients. CONCLUSIONS: PE ratio reflects the ability to equalize pressure with the preset height of the EVD and differs substantially between TBI and non-TBI patients. A high PE ratio likely indicates CSF outflow obstruction effectively treated by CSF diversion, while a lower PE ratio occurs when cerebral swelling predominates. Further studies could assess whether the PE ratio would be useful as a surrogate marker for cerebral edema or the state of intracranial compliance.

A medulloblastoma showing an unusually long doubling time: reflection of its singular nature.

CASE DESCRIPTION: In this paper, we present a case of a 4-year-old male diagnosed with a desmoplastic, SHH-type medulloblastoma. Retrospectively, we discovered that the patient underwent an MRI scan at 21 months for reasons unrelated, revealing a T1-enhanced lesion at the vermis, later recognized as the source of the tumor. This unique case provides us with a glimpse into the natural history of this tumor. Our ability to measure tumor volume at two defined time points, 31 months apart, enabled us to deduce the tumor's doubling time. This is defined as the time of one cell cycle divided by the amount of cycling cells, multiplied by cell loss factor. Potential doubling time (Tpot) and actual doubling time (Td), calculated using the Gompertzian model, are the most clinically relevant with regard to a tumor's response to radiotherapy. Here, we show an actual doubling-time (Td) of 78 days, and an extrapolated tumor diameter at the time of birth of 0.25 mm. CLINICAL RELEVANCE: These results both support the medulloblastoma's embryonic origin, and indicating a threefold longer actual doubling time when compared to previous studies. Taking into account the reported range of medulloblastoma potential doubling time, we deduced a cell loss factor of between 48.9 and 95.5 %. These percentages fall in line with other malignant tumors. Although limited due to the obvious reliance on only two points in time and using the Gompertzian model to complete the remainder, to the best of our knowledge, this is the longest follow-up period reported for medulloblastoma. We have described how a unique turn of events enabled us to get a glimpse into the in situ development of a medulloblastoma over a 31-month period. Regarded sometimes as an idiosyncratic tumor comprised of an array of molecular changes, the complexity of medulloblastoma is displayed here, by revealing for the first time an actual doubling time three- to fourfold the previously known length.

MRI features have a role in pre-surgical planning of colloid cyst removal.

BACKGROUND: Endoscopic resection is becoming a well-established treatment option for patients with colloid cysts of the third ventricle. A disadvantage of this approach is the decreased ability to resect cysts in their entirety. Correlations between magnetic resonance imaging (MRI) features and cyst content could potentially help surgeons decide on the extent of resection and approach. We attempted to identify a correlation between patients' MRI imaging patterns and difficult cyst removal, post-operative adverse outcomes and the need for cerebrospinal fluid (CSF) diversion, in order to detect markers that may affect pre-surgical planning. METHOD: A retrospective examination of all patients' records that underwent a colloid cyst excision attempt at our institution between 2001 and 2014, and which had a minimum 1-year follow-up was compiled. RESULTS: Of the 25 patients fulfilling the criteria, we found cysts with a low T2 signal, specifically when combined with high T1 signal, to be significantly correlated with piecemeal, difficult removals. Correlation was also found between high T2 signal cysts and pre-operative hydrocephalus. Among patients that had pre-existing hydrocephalus, those that required a piecemeal removal possessed a strong trend towards a need for subsequent shunting. CONCLUSIONS: We found specific MRI features suggestive of difficult cyst excision. In a subgroup of patients with pre-operative hydrocephalus and imaging features suggestive of difficult removal, significantly higher rates of shunting were observed. We therefore recommend an open approach in cases of low T2, high T1 signal cysts with a diameter of over 15 mm, or CSF shunting in poor surgical candidates. Smaller cysts, with a low T1 signal, a high T2 signal and pre-operative hydrocephalus, constitute a subgroup in which we recommend endoscopic intervention as the procedure of choice.

Neurovascular Interventions for Neurotrauma: From Treatment of Injured Vessels to Treatment of the Injured Brain?

Traumatic brain injury is often associated with a direct or secondary neurovascular pathology. In this review, we present recent advancements in endovascular neurosurgery that enable accurate and effective vessel reconstruction with emphasis on its role in early diagnosis, the expanding use of flow diversion in pseudoaneurysms, and traumatic arteriovenous fistulas. In addition, future directions in which catheter-based interventions could potentially affect traumatic brain injury are described: targeting blood brain barrier integrity using the advantages of intra-arterial drug delivery of blood brain barrier stabilizers to prevent secondary brain edema, exploring the impact of endovascular venous access as a means to modulate venous outflow in an attempt to reduce intracranial pressure and augment brain perfusion, applying selective intra-arterial hypothermia as a neuroprotection method mitigating some of the risks conferred by systemic cooling, trans-vessel wall delivery of regenerative therapy agents, and shifting attention using multimodal neuromonitoring to post-traumatic vasospasm to further characterize the role it plays in secondary brain injury. Thus, we believe that the potential of endovascular tools can be expanded because they enable access to the "highways" governing perfusion and flow and call for further research focused on exploring these routes because it may contribute to novel endovascular approaches currently used for treating injured vessels, harnessing them for treatment of the injured brain.

Limitation of cerebral blood flow by increased venous outflow resistance in elevated ICP.

Extensive investigation and modeling efforts have been dedicated to cerebral pressure autoregulation, which is primarily regulated by the ability of the cerebral arterioles to change their resistance and modulate cerebral blood flow (CBF). However, the mechanisms by which elevated intracranial pressure (ICP) leads to increased resistance to venous outflow have received less attention. We modified our previously described model of intracranial fluid interactions with a newly developed model of a partially collapsed blood vessel, which we termed the "flow control zone" (FCZ). We sought to determine the degree to which ICP elevation causing venous compression at the FCZ becomes the main parameter limiting CBF. The FCZ component was designed using nonlinear functions representing resistance as a function of cross-sectional area and the pressure-volume relations of the vessel wall. We used our previously described swine model of cerebral edema with graduated elevation of ICP to calculate venous outflow resistance and a newly defined parameter, the cerebral resistance index (CRI), which is the ratio between venous outflow resistance and cerebrovascular resistance. Model simulations of cerebral edema and increased ICP led to increased venous outflow resistance. There was a close similarity between model predictions of venous outflow resistance and experimental results in the swine model (cross-correlation coefficient of 0.97, a mean squared error of 0.087, and a mean absolute error of 0.15). CRI was strongly correlated to ICP in the swine model (r2 = 0.77, P = 0.00012, 95% confidence interval [0.15, 0.45]). A CRI value of 0.5 was associated with ICP values above clinically significant thresholds (24 mmHg) in the swine model and a diminished capacity of changes in arteriolar resistance to influence flow in the mathematical model. Our results demonstrate the importance of venous compression at the FCZ in determining CBF when ICP is elevated. The cerebral resistance index may provide an indication of when compression of venous outflow becomes the dominant factor in limiting CBF following brain injury.NEW & NOTEWORTHY The goal of this study was to investigate the effects of venous compression caused by elevated intracranial pressure (ICP) due to cerebral edema, validated through animal experiments. The flow control zone model highlights the impact of cerebral venous compression on cerebral blood flow (CBF) during elevated ICP. The cerebral venous outflow resistance-to-cerebrovascular resistance ratio may indicate when venous outflow compression becomes the dominant factor limiting CBF. CBF regulation descriptions should consider how arterial or venous factors may predominantly influence flow in different clinical scenarios.

Estimating intracranial parameters using an inverse mathematical model with viscoelastic elements that closely predicts complex ICP morphologies.

The quantitative relationship between arterial blood pressure (ABP) and intracranial pressure (ICP) waveforms has not been adequately explained. We hypothesized that the ICP waveform results from interferences between propagating and reflected pressure waves occurring in the cranium following the initiating arterial waveform. To demonstrate cranial effects on interferences between waves and generation of an ICP waveform morphology, we modified our previously reported mathematical model to include viscoelastic elements that affect propagation velocity. Using patient data, we implemented an inverse model methodology to generate simulated ICP waveforms in response to given ABP waveforms. We used an open database of traumatic brain injury patients and studied 65 pairs of ICP and ABP waveforms from 13 patients (five pairs from each). Incorporating viscoelastic elements into the model resulted in model-generated ICP waveforms that very closely resembled the measured waveforms with a 16-fold increase in similarity index relative to the model with only pure elasticity elements. The mean similarity index for the pure elasticity model was 0.06 ± 0.12 SD, compared to 0.96 ± 0.28 SD for the model with viscoelastic components. The normalized root mean squared error (NRMSE) improved substantially for the model with viscoelastic elements compared to the model with pure elastic elements (NRMSE of 2.09% ± 0.62 vs. 15.2% ± 4.8, respectively). The ability of the model to generate complex ICP waveforms indicates that the model may indeed reflect intracranial dynamics. Our results suggest that the model may allow the estimation of intracranial biomechanical parameters with potential clinical significance. It represents a first step in the estimation of inaccessible intracranial parameters.

Endovascular and medical management strategies for carotid-cavernous fistulas: A safety and efficacy analysis.

BACKGROUND: Carotid-cavernous fistulas (CCFs) are complex arteriovenous shunting lesions of the cavernous sinus with diverse clinical presentations. This study aimed to analyze clinical outcomes and differentiate patients treated with conservative observation versus those needing endovascular intervention. METHODS: A retrospective analysis of 84 patients with angiographically confirmed CCF was conducted from 2000 to 2022. Endovascular treatment decisions were made at the discretion of neurointerventionalists. Clinical and angiographic data were collected, including Barrow CCF classification and treatment outcomes. RESULTS: Patients managed conservatively (n = 17) had longer symptom duration (165 vs 42 days) and more indirect CCF (100% vs 68%) compared to those treated with endovascular embolization (n = 67). High-risk clinical symptoms, including proptosis, diplopia, decreased visual acuity, and chemosis, were more common in the embolization group. Cortical venous reflux and ophthalmic venous reflux were more prevalent in the embolization group (39% and 91%, respectively). Overall, 31% of embolized CCFs required retreatment, mainly Barrow type D lesions (65%). Transvenous coil embolization was the primary technique used (78%), followed by feeder artery embolization (16%), and internal carotid artery flow diversion (8%). CONCLUSION: In selected CCF patients without high-risk symptoms or angiographic features, conservative observation is a safe and effective alternative to endovascular embolization. High-risk symptoms and angiographic features favor endovascular intervention. Complications were rare, and most were transient, emphasizing the safety of endovascular management. Longitudinal angiographic and ophthalmologic surveillance is essential for monitoring fistula persistence or recurrence.