Neurological Outcomes Following Craniotomy for Extracorporeal Membrane Oxygenation-Associated Intracranial Hemorrhage: Case Series and Literature Review.

BACKGROUND: Intracranial hemorrhage (ICH) is a potential complication associated with extracorporeal membrane oxygenation (ECMO), which has been increasingly utilized in recent years. A paucity of data exists describing patient outcomes following invasive neurosurgical interventions in patients receiving ECMO therapy. The purpose of this study was to assess the clinical and functional outcomes in patients who underwent cranial neurosurgery for the management of an ECMO-associated intracranial complication. METHODS: This was a single-institution retrospective review of adult patients who underwent craniotomy or craniectomy after sustaining an intracranial hemorrhagic complication of ECMO therapy from 2008 to 2023. Anticoagulation status, operative indication, surgical details, postoperative course, and functional outcome were recorded. A systematic review of the prior literature was performed to contextualize our institutional results within previous reports. RESULTS: Four adult patients were identified at our institution who underwent craniotomy or craniectomy for the neurosurgical management of an ECMO-associated ICH. One patient (25%) ultimately made a satisfactory recovery (Modified Rankin Scale score 3 at 1 year). The surviving patient had a notably higher Glasgow Coma Scale (7T vs. 3T), had not received anticoagulation at the time of surgery, and did not experience postoperative reaccumulation or expansion of their hemorrhage, distinguishing factors from the other 3 included. Review of the existing literature identified 15 adult patients who underwent craniotomy while receiving ECMO therapy, of which 4 (26.7%) had a long-term favorable neurologic outcome. CONCLUSIONS: The overall prognosis following neurosurgical intervention for the management of ECMO-associated intracranial complications was poor in our case series, which was corroborated by our literature review.

The incidence of infratentorial arteriovenous malformation-associated aneurysms: an institutional case series and systematic literature review.

BACKGROUND: Arteriovenous malformation (AVM)-associated aneurysms represent a high-risk feature predisposing them to rupture. Infratentorial AVMs have been shown to have a greater incidence of associated aneurysms, however the existing data is outdated and biased. The aim of our research was to compare the incidence of supratentorial vs infratentorial AVM-associated aneurysms. METHODS: Patients were identified from our institutional AVM registry, which includes all patients with an intracranial AVM diagnosis since 2000, regardless of treatment. Records were reviewed for clinical details, AVM characteristics, nidus location (supratentorial or infratentorial), and presence of associated aneurysms. Statistical comparisons were made using Fisher's exact or Wilcoxon rank sum tests as appropriate. Multivariable logistic regression analysis determined independent predictors of AVM-associated aneurysms. As a secondary analysis, a systematic literature review was performed, where studies documenting the incidence of AVM-associated aneurysms stratified by location were of interest. RESULTS: From 2000-2024, 706 patients with 720 AVMs were identified, of which 152 (21.1%) were infratentorial. Intracranial hemorrhage was the most common AVM presentation (42.1%). The incidence of associated aneurysms was greater in infratentorial AVMs compared with supratentorial cases (45.4% vs 20.1%; P<0.0001). Multivariable logistic regression demonstrated that infratentorial nidus location was the singular predictor of an associated aneurysm, odds ratio: 2.9 (P<0.0001). Systematic literature review identified eight studies satisfying inclusion criteria. Aggregate analysis indicated infratentorial AVMs were more likely to harbor an associated aneurysm (OR 1.7) and present as ruptured (OR 3.9), P<0.0001. CONCLUSIONS: In this modern consecutive patient series, infratentorial nidus location was a significant predictor of an associated aneurysm and hemorrhagic presentation.

Maturation of germinal center B cells after influenza virus vaccination in humans.

Germinal centers (GC) are microanatomical lymphoid structures where affinity-matured memory B cells and long-lived bone marrow plasma cells are primarily generated. It is unclear how the maturation of B cells within the GC impacts the breadth and durability of B cell responses to influenza vaccination in humans. We used fine needle aspiration of draining lymph nodes to longitudinally track antigen-specific GC B cell responses to seasonal influenza vaccination. Antigen-specific GC B cells persisted for at least 13 wk after vaccination in two out of seven individuals. Monoclonal antibodies (mAbs) derived from persisting GC B cell clones exhibit enhanced binding affinity and breadth to influenza hemagglutinin (HA) antigens compared with related GC clonotypes isolated earlier in the response. Structural studies of early and late GC-derived mAbs from one clonal lineage in complex with H1 and H5 HAs revealed an altered binding footprint. Our study shows that inducing sustained GC reactions after influenza vaccination in humans supports the maturation of responding B cells.

Risk assessment of early therapeutic anticoagulation following cranial surgery: an institutional case series.

OBJECTIVE: Postoperative thrombotic complications represent a unique challenge in cranial neurosurgery as primary treatment involves therapeutic anticoagulation. The decision to initiate therapy and its timing is nuanced, as surgeons must balance the risk of catastrophic intracranial hemorrhage (ICH). With limited existing evidence to guide management, current practice patterns are subjective and inconsistent. The authors assessed their experience with early therapeutic anticoagulation (≤ 7 days postoperatively) initiation for thrombotic complications in neurosurgical patients undergoing cranial surgery to better understand the risks of catastrophic ICH. METHODS: Adult patients treated with early therapeutic anticoagulation following cranial surgery were considered. Anticoagulation indications were restricted to thrombotic or thromboembolic complications. Records were retrospectively reviewed for demographics, surgical details, and anticoagulation therapy start. The primary outcome was the incidence of catastrophic ICH, defined as ICH resulting in reoperation or death within 30 days of anticoagulation initiation. As a secondary outcome, post-anticoagulation cranial imaging was reviewed for new or worsening acute blood products. Fisher's exact and Wilcoxon rank-sum tests were used to compare cohorts. Cumulative outcome analyses were performed for primary and secondary outcomes according to anticoagulation start time. RESULTS: Seventy-one patients satisfied the inclusion criteria. Anticoagulation commenced on mean postoperative day (POD) 4.3 (SD 2.2). Catastrophic ICH was observed in 7 patients (9.9%) and was associated with earlier anticoagulation initiation (p = 0.02). Of patients with catastrophic ICH, 6 (85.7%) had intra-axial exploration during their index surgery. Patients with intra-axial exploration were more likely to experience a catastrophic ICH postoperatively compared to those with extra-axial exploration alone (OR 8.5, p = 0.04). Of the 58 patients with postoperative imaging, 15 (25.9%) experienced new or worsening blood products. Catastrophic ICH was 9 times more likely with anticoagulation initiation within 48 hours of surgery (OR 8.9, p = 0.01). The cumulative catastrophic ICH risk decreased with delay in initiation of anticoagulation, from 21.1% on POD 2 to 9.9% on POD 7. Concurrent antiplatelet medication was not associated with either outcome measure. CONCLUSIONS: The incidence of catastrophic ICH was significantly increased when anticoagulation was initiated within 48 hours of cranial surgery. Patients undergoing intra-axial exploration during their index surgery were at higher risk of a catastrophic ICH.

The obesity paradox and ventriculoperitoneal shunting in aneurysmal subarachnoid hemorrhage patients undergoing microsurgical clipping.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) can be devastating. Identifying predisposing factors is paramount in reducing aSAH-related mortality. Obesity's negative impact on health is well-established. However, the controversial "obesity paradox" in neurosurgery suggests that obesity may confer a survival advantage in SAH. We hypothesized that obesity would have a negative impact on outcomes following surgical clipping in aSAH. METHODS: A single-institution retrospective review was performed of aSAH patients undergoing surgical clipping from 2017 to 2021. Demographics and clinically relevant variables were collected. Obesity was defined as body mass index >30. Primary outcome was death or severe disability (mRS 4-6) at last follow-up. Secondary outcome was VPS placement. Multivariable Cox proportional-hazards model identified predictors of poor outcome. Kaplan-Meier curves identified survivorship differences between obese and non-obese patients. RESULTS: Poor outcome occurred in 11 of 52 total patients (21.2 %). There were no differences in demographics or distribution of Hunt Hess (HH), modified Fisher Grade (mFG), or external ventricular drain (EVD) placement between obese and non-obese patients. On univariate analysis, hypertension, older age, and non-obesity were predictive of poor outcome. On multivariable analysis, only obesity remained significant, suggesting a protective effect from poor outcome (HR 0.45 [0.21-0.95], p = 0.037). VPS placement occurred in 6 (11.5 %) patients for which obesity was not a significant predictor. CONCLUSIONS: Obesity may have a protective effect against poor outcome following surgical clipping in aSAH. Additionally, obesity does not appear to increase rate of EVD conversion to VPS. Thus, our study suggests that obesity should not preclude patients from open surgical intervention when clinically appropriate.

Repeat Flow Diversion for Retreatment of Incompletely Occluded Large Complex Symptomatic Cerebral Aneurysms: A Retrospective Case Series.

BACKGROUND AND OBJECTIVES: Data regarding radiographic occlusion rates after repeat flow diversion after initial placement of a flow diverter (FD) in large intracranial aneurysms are limited. We report clinical and angiographic outcomes on 7 patients who required retreatment with overlapping FDs after initial flow diversion for large intracranial aneurysms. METHODS: We performed a retrospective review of a prospectively maintained database of cerebrovascular procedures performed at our institution from 2017 to 2021. We identified patients who underwent retreatment with overlapping FDs for large (>10 mm) cerebral aneurysms after initial flow diversion. At last angiographic follow-up, occlusion grade was evaluated using the O'Kelly-Marotta (OKM) grading scale. RESULTS: Seven patients (median age 57 years) with cerebral aneurysms requiring retreatment were identified. The most common aneurysm location was the ophthalmic internal carotid artery (n = 3) and basilar trunk (n = 3). There were 4 fusiform and 3 saccular aneurysms. The median aneurysm width was 18 mm; the median neck size for saccular aneurysms was 7 mm; and the median dome-to-neck ratio was 2.8. The median time to retreatment was 9 months, usually due to symptomatic mass effect. After retreatment, the median clinical follow-up was 36 months, MRI/magnetic resonance angiography follow-up was 15 months, and digital subtraction angiography follow-up was 14 months. Aneurysm occlusion at last angiographic follow-up was graded as OKM A (total filling, n = 1), B (subtotal filling, n = 2), C (early neck remnant, n = 3), and D (no filling, n = 0). All patients with symptomatic improvement were OKM C, whereas patients with worsened symptom burden were OKM A or B. Two patients required further open surgical management for definitive management of the aneurysm remnant. CONCLUSION: Although most patients demonstrated a decrease in aneurysm remnant size, many had high-grade persistent filling (OKM grades A or B) in this subset of mostly large fusiform aneurysms. Larger studies with longer follow-up are warranted to optimize treatment strategies for atypical aneurysm remnants after repeat flow diversion.

Treatment outcomes for ARUBA-eligible brain arteriovenous malformations: a comparison of real-world data from the NVQI-QOD AVM registry with the ARUBA trial.

BACKGROUND: Significant controversy exists about the management of unruptured cerebral arteriovenous malformations (AVMs). Results from A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) suggested that intervention increases the risk of stroke/death compared with medical management. However, numerous study limitations raised concerns about the trial's generalizability. OBJECTIVE: To assess the rate of stroke/death and functional outcomes in ARUBA-eligible patients from a multicenter database, the Neurovascular Quality Initiative-Quality Outcomes Database (NVQI-QOD). METHODS: We performed a retrospective analysis of prospectively collected data of ARUBA-eligible patients who underwent intervention at 18 participating centers. The primary endpoint was stroke/death from any cause. Secondary endpoints included neurologic, systemic, radiographic, and functional outcomes. RESULTS: 173 ARUBA-eligible patients underwent intervention with median follow-up of 269 (25-722.5) days. Seventy-five patients received microsurgery±embolization, 37 received radiosurgery, and 61 received embolization. Baseline demographics, risk factors, and general AVM characteristics were similar between groups. A total of 15 (8.7%) patients experienced stroke/death with no significant difference in primary outcome between treatment modalities. Microsurgery±embolization was more likely to achieve AVM obliteration (P<0.001). Kaplan-Meier survival curves demonstrated no difference in overall death/stroke outcomes between the different treatment modalities' 5-year period (P=0.087). Additionally, when compared with the ARUBA interventional arm, our patients were significantly less likely to experience death/stroke (8.7% vs 30.7%; P<0.001) and functional impairment (mRS score ≥2 25.4% vs 46.2%; P<0.01). CONCLUSION: Our results suggest that intervention for unruptured brain AVMs at comprehensive stroke centers across the United States is safe.

Prognosticators of Functional Outcome After Supratentorial Minimally Invasive Intracranial Hemorrhage Evacuation With Tubular Retractor Systems.

BACKGROUND AND OBJECTIVES: Prognosticators of good functional outcome after minimally invasive surgical (MIS) intracranial hemorrhage (ICH) evacuation are poorly defined. This study aims to investigate clinical and radiographic prognosticators of poor functional outcome after MIS evacuation of ICH with tubular retractor systems. METHODS: Single-center retrospective review of adult (age ≥18 years) patients who underwent surgical evacuation of a spontaneous supratentorial ICH evacuation using tubular retractors from 2013 to 2022 was performed. Clinical and radiographic factors, such as antiplatelet/anticoagulant use, initial NIH Stroke Scale, ICH score, premorbid modified Rankin Scale (mRS), intraventricular hemorrhage (IVH) severity according to the modified Graeb scale, and preoperative/postoperative ICH volume, were collected. The main outcome was poor functional outcome, defined as mRS score of 4-6 within 1 year postoperatively. RESULTS: Eighty-eight patients were included. Clinical follow-up data were available for 64 (73%) patients. Of those, 43 (67%) had a poor functional outcome. On multivariate Cox regression, postoperative ICH volume ≥15 mL (hazard ratio [HR] = 2.46 [95% CI: 1.25-4.87]; P = .010) and higher modified Graeb score (HR = 1.04 [95% CI: 1-1.1]; P = .035] significantly increased the risk of poor functional outcome. Elevated postoperative ICH volume was predicted by the presence of lobar ICH (vs nonlobar, OR = 3.32 [95% CI: 1.01-11.55]; P = .043) and higher preoperative ICH volume (OR = 1.05 [1.02-1.08]; P < .001). A minimum of 60% ICH evacuation yielded an improvement in mRS 4-6 rates (HR 0.3 [95% CI: 0.1-0.8], P = .013). In patients without IVH and with a >80% ICH evacuation, the rate of mRS 4-6 was 42% compared with 67% in the whole patient sample ( P = .017). CONCLUSION: Increased IVH volumes and residual postoperative ICH volumes are associated with poor functional outcome after MIS ICH evacuation. Postoperative ICH volume was associated with lobar ICH location as well as preoperative ICH volume. These factors may help to prognosticate patient outcomes and improve selection criteria for MIS ICH evacuation techniques.

Flow diversion for the treatment of intracranial bifurcation aneurysms: a systematic review and meta-analysis.

BACKGROUND: Flow diversion (FD: flow diversion, flow diverter) is an endovascular treatment for many intracranial aneurysm types; however, limited reports have explored the use of FDs in bifurcation aneurysm management. We analyzed the safety and efficacy of FD for the management of intracranial bifurcation aneurysms. METHODS: A systematic review identified original research articles that used FD for treating intracranial bifurcation aneurysms. Articles with >4 patients that reported outcomes on the use of FDs for the management of bifurcation aneurysms along the anterior communicating artery (AComA), internal carotid artery terminus (ICAt), basilar apex (BA), or middle cerebral artery bifurcation (MCAb) were included. Meta-analysis was performed using a random effects model. RESULTS: 19 studies were included with 522 patients harboring 534 bifurcation aneurysms (mean size 9 mm, 78% unruptured). Complete aneurysmal occlusion rate was 68% (95% CI 58.7% to 76.1%, I2=67%) at mean angiographic follow-up of 16 months. Subgroup analysis of FD as a standalone treatment estimated a complete occlusion rate of 69% (95% CI 50% to 83%, I2=38%). The total complication rate was 22% (95% CI 16.7% to 28.6%, I2=51%), largely due to an ischemic complication rate of 16% (95% CI 10.8% to 21.9%, I2=55%). The etiologies of ischemic complications were largely due to jailed artery hypoperfusion (47%) and in-stent thrombosis (38%). 7% of patients suffered permanent symptomatic complications (95% CI 4.5% to 9.8%, I2=6%). CONCLUSION: FD treatment of bifurcation aneurysms has a modest efficacy and relatively unfavorable safety profile. Proceduralists may consider reserving FD as a treatment option if no other surgical or endovascular therapy is deemed feasible.

A novel endoleak classification for intracranial aneurysm flow diversion: A retrospective case series.

BACKGROUND: Although flow diversion (FD) is safe and effective in the treatment of intracranial aneurysms, a subset tends to continue filling on serial angiography. Risk factors for failed flow diversion include old age, large aneurysm size, and overstenting an adjacent end-arterial vessel. The hemodynamic modes of persistent aneurysm filling, or 'endoleaks', after FD are poorly understood. This study aims to characterize the various types of endoleaks following aneurysmal FD. METHODS: We performed a retrospective review of a prospectively maintained database of all endovascular procedures performed at a single institution between 2017 and 2021. Patients were included if they demonstrated evidence of unique modes of intracranial aneurysm filling after FD. Data regarding treatment, follow-up angiography, as well as clinical course were collected. RESULTS: Five patients (mean age 50 years, four females) were included with mean 19-month angiographic follow-up. Five major endoleak types are proposed: Type 1 - due to graft porosity (A - low flow, B - high flow), Type 2 -through an overstented branch vessel, Type 3 - via stent migration no longer covering aneurysmal neck, Type 4 - endoleak due to malapposition of the stent wall, and Type 5 - endoleak via collateralization from adjacent blood vessels. All endoleak types were represented, except for the Type 4 endoleak. CONCLUSION: We propose an endoleak classification scheme to describe the hemodynamic modes of failure following FD of intracranial aneurysms. Future studies are needed to evaluate the natural history of aneurysmal filling following FD and retreatment success according to endoleak type.

Mechanical thrombectomy for acute large vessel occlusion stroke beyond 24 h.

BACKGROUND: Multiple trials have shown that mechanical thrombectomy (MT) is superior to medical therapy. However, no robust evidence is available regarding MT beyond 24 h. In this study, we aimed to determine the safety and efficacy of endovascular stroke therapy in this late window. METHODS: We conducted a retrospective study of prospectively collected data of patients who met extended window trial criteria, but underwent MT beyond 24 h. Safety and efficacy outcomes included symptomatic intracerebral hemorrhage (sICH), procedural complications, number of passes, successful recanalization (mTICI 2b - 3), delta (Δ) NIHSS (baseline-discharge), and favorable outcomes (mRS 0-2 at 90 days). RESULTS: A total of 39 patients were included with a median age of 69 years (IQR 61.5, 73.5); 54% were females. Hypertension was present in 76% of patients; 23% were smokers. Half of the patients had M1 occlusion (48.7%). Median preprocedural NIHSS was 11 (IQR 7.0, 19.5). Successful revascularization was achieved in 87%; median number of passes was 2 (IQR 1.0, 3.0). Median ΔNIHSS was 3.0 (IQR -1.5, 8.0). Favorable outcome was achieved in 49% (95% CI: 34%-64%), and 95% were free of complications. A total of 3 patients (7.7%) had sICH. In an exploratory analysis, posterior circulation occlusion was associated with higher mRS at 90 days (OR: 14.7, p = 0.016). Favorable discharge facility was associated with lower mRS at 90 days (OR: 0.11, p = 0.004). CONCLUSIONS: Our study showed comparable clinical outcomes of MT beyond 24 h compared to MT trials within 24 h in patients with favorable imaging profile, especially in anterior circulation occlusions.

Diagnostic yield of cerebral angiography for intracranial hemorrhage in young patients: A single-center retrospective analysis.

BACKGROUND: Intracranial hemorrhage (ICH) secondary to hypertension (HTN) classically occurs in the basal ganglia, cerebellum, or pons. Vascular lesions such as aneurysms or arteriovenous malformations (AVMs) are more common in younger patients. We investigated the utility of diagnostic subtraction angiography (DSA) in young hypertensive patients with non-lobar ICH. METHODS: A retrospective review (2013-2022) identified young (18-60 years) patients who underwent DSA for ICH. HTN history, ICH location, presence/absence of subarachnoid hemorrhage (SAH), and computed tomography angiography (CTA) findings were collected. The main outcome was DSA-positivity, defined as presence of an AVM, aneurysm, Moyamoya disease, reversible cerebral vasoconstriction syndrome, or dural arteriovenous fistula on DSA. RESULTS: Two hundred sixty patients were included, and the DSA-positivity rate was 19%.DSA-positivity was lower in hypertensive patients with ICHs in the cerebellum, pons, or basal ganglia compared to the rest of the patient sample (9% vs 26%, p = 0.0002, Fisher's exact test). We developed the ICH-Angio score (0-5 points) based on CTA findings, ICH location, HTN history, and presence of SAH to predict risk of underlying vascular lesions. DSA-positivity was lower in those with a score of 0 (0/62; 0%) compared to a score of 1 (5/52; 10%), 2 (17/48; 35%), 3 (10/20; 50%), 4 (5/6; 83%), or 5 (3/3; 100%). CONCLUSION: The ICH-Angio score was able to non-invasively rule out an underlying vascular etiology for ICH in up to one-third of patients. HTN, ICH location, CTA findings, and associated SAH can identify patients at low risk for harboring underlying vascular lesions.

Flow Diversion as Destination Treatment of Intracranial Mycotic Aneurysms: A Retrospective Case Series.

BACKGROUND: Mycotic aneurysms represent a rare type of intracranial aneurysm. Treatment options usually consist of coiling, clipping, or liquid embolization. Data regarding outcomes after flow diversion of mycotic aneurysms are sparse. OBJECTIVE: To present a single-center case series regarding our experience with FD as definitive treatment for ruptured mycotic aneurysms initially treated with coil embolization. METHODS: We retrospectively reviewed a prospectively maintained database of all cerebrovascular procedures performed at a single institution between 2017 and 2021 for cases that used FD for the management of intracranial mycotic aneurysms. Prospectively collected data included patient demographics, medical history, rupture status, aneurysm morphology, aneurysm location, and periprocedural complications. The main outcomes included neurological examination and radiographic occlusion rate on cerebral digital subtraction angiography. RESULTS: Three patients with 4 ruptured mycotic aneurysms that were initially treated with coil embolization were identified that required retreatment. The aneurysms were located along the middle cerebral artery bifurcation (n = 2), posterior cerebral artery P1/2 junction (n = 1), and basilar artery apex (n = 1), which all demonstrated recurrence after initial coil embolization. Successful retreatment using flow diverting stents was performed in all 3 patients. At the last angiographic follow-up, all aneurysms demonstrated complete occlusion. No patients suffered new periprocedural complications or neurological deficits after FD. CONCLUSION: Flow-diverting stents may be an effective treatment option for intracranial mycotic aneurysms that are refractory to previous endovascular coiling. Future studies are warranted to establish the associated long-term safety and clinical efficacy.

Surgical Resection of Deep-Seated Arteriovenous Malformations Through Stereotactically Guided Tubular Retractor Systems: A Case Series.

BACKGROUND: Arteriovenous malformations (AVMs) in the subcortical and/or periventricular regions can cause significant intraventricular and intracranial hemorrhage. These AVMs can pose a unique surgical challenge because traditional, open approaches to the periventricular region require significant cortical/white matter retraction to establish sufficient operative corridors, which may result in risk of neurological injury. Minimally invasive tubular retractor systems represent a novel, feasible surgical option for treating deep-seated AVMs. OBJECTIVE: To explore 5 cases of NICO BrainPath-assisted resection of subcortical/periventricular AVMs. METHODS: Five patients from a single institution were operated on for deep-seated AVMs using tubular retractor systems. Collected data included demographics, AVM specifications, preoperative neurological status, postoperative neurological status, and postoperative/intraoperative angiogram results. RESULTS: Five patients, ranging from age 10 to 45 years, underwent mini-craniotomy for stereotactically guided tubular retractor-assisted AVM resection using neuronavigation for selecting a safe operative corridor. No preoperative embolization was necessary. Mean maximum AVM nidal diameter was 8.2 mm. All deep-seated AVMs were completely resected without complications. All AVMs demonstrated complete obliteration on intraoperative angiogram and on 6-month follow-up angiogram. CONCLUSION: Minimally invasive tubular retractors are safe and present a promising surgical option for well-selected deep-seated AVMs. Furthermore, study may elucidate whether tubular retractors improve outcomes after microsurgical AVM resection secondary to mitigation of iatrogenic retraction injury risk.

Assessment of Cerebral Autoregulation Using Invasive and Noninvasive Methods of Intracranial Pressure Monitoring.

BACKGROUND: Pulse amplitude index (PAx), a descriptor of cerebrovascular reactivity, correlates the changes of the pulse amplitude of the intracranial pressure (ICP) waveform (AMP) with changes in mean arterial pressure (MAP). AMP relies on cerebrovascular compliance, which is modulated by the state of the cerebrovascular reactivity. PAx can aid in prognostication after acute brain injuries as a tool for the assessment of cerebral autoregulation and could potentially tailor individual management; however, invasive measurements are required for its calculation. Our aim was to evaluate the relationship between noninvasive PAx (nPAx) derived from a novel noninvasive device for ICP monitoring and PAx derived from gold standard invasive methods. METHODS: We retrospectively analyzed invasive ICP (external ventricular drain) and non-invasive ICP (nICP), via mechanical extensometer (Brain4Care Corp.). Invasive and non-invasive ICP waveform morphology data was collected in adult patients with brain injury with arterial blood pressure monitoring. The time series from all signals were first treated to remove movement artifacts. PAx and nPAx were calculated as the moving correlation coefficients of 10-s averages of AMP or non-invasive AMP (nAMP) and MAP. AMP/nAMP was determined by calculating the fundamental frequency amplitude of the ICP/nICP signal over a 10-s window, updated every 10-s. We then evaluated the relationship between invasive PAx and noninvasive nPAx using the methods of repeated-measures analysis to generate an estimate of the correlation coefficient and its 95% confidence interval (CI). The agreement between the two methods was assessed using the Bland-Altman test. RESULTS: Twenty-four patients were identified. The median age was 53.5 years (interquartile range 40-70), and intracranial hemorrhage (84%) was the most common etiology. Twenty-one (87.5%) patients underwent mechanical ventilation, and 60% were sedated with a median Glasgow Coma Scale score of 8 (7-15). Mean PAx was 0.0296 ± 0.331, and nPAx was 0.0171 ± 0.332. The correlation between PAx and nPAx was strong (R = 0.70, p < 0.0005, 95% CI 0.687-0.717). Bland-Altman analysis showed excellent agreement, with a bias of - 0.018 (95% CI - 0.026 to - 0.01) and a localized regression trend line that did not deviate from 0. CONCLUSIONS: PAx can be calculated by conventional and noninvasive ICP monitoring in a statistically significant evaluation with strong agreement. Further study of the applications of this clinical tool is warranted, with the goal of early therapeutic intervention to improve neurologic outcomes following acute brain injuries.

Comparative effectiveness of stent-assisted coiling and Woven EndoBridge embolization for the treatment of unruptured wide-neck bifurcation intracranial aneurysms.

OBJECTIVE: Woven EndoBridge (WEB) intrasaccular flow disruptors and stent-assisted coiling (SAC) are viable endovascular treatment options for wide-neck bifurcation intracranial aneurysms (WNBAs). Data directly comparing these two treatment options are limited. The authors aimed to compare radiographic occlusion rates and complication profiles between patients who received WEB and those who received SAC for WNBAs. METHODS: Retrospective review of a prospectively maintained cerebrovascular procedural database was performed at a single academic medical center between 2017 and 2021. Patients were included if they underwent WEB embolization or SAC of an unruptured WNBA. SAC patients were propensity matched to WEB-embolized patients on the basis of aneurysm morphology. Complete and adequate (complete occlusion or residual neck remnant) occlusion rates at last angiographic follow-up, as well as periprocedural complications, were compared between the two groups. A cost comparison was performed for a typical 5-mm WNBA treated with WEB versus SAC by using manufacturer-suggested retail prices. RESULTS: Thirty-five WEB and 70 SAC patients were included. Aneurysm width, neck size, and dome-to-neck ratio were comparable between groups. Follow-up duration was significantly longer in the SAC group (median [interquartile range] 545 [202-834] days vs 228 [177-494] days, p < 0.001, Mann-Whitney U-test). Complete (66% of WEB patients vs 69% of SAC patients) and adequate (94% WEB vs 91% SAC) occlusion rates were similar between groups at the last available angiographic follow-up (p = 0.744, chi-square test). Complete occlusion rates were comparable on Cox regression analysis after correction for follow-up duration (hazard ratio 1.5, 95% CI 0.8-3.1). Average time to residual aneurysm or neck formation was not statistically different between treatment groups (613 days for SAC patients vs 347 days for WEB patients, p = 0.225, log-rank test). Periprocedural complications trended higher in the SAC group (0% WEB vs 9% SAC, p = 0.175, Fisher exact test), although this finding was not significant. The equipment costs for a typical SAC case were estimated at $18,950, whereas the costs for a typical WEB device case were estimated at $18,630. CONCLUSIONS: Midterm complete and adequate occlusion rates were similar between patients treated with WEB and those treated with SAC. Given these comparable outcomes, there may be equipoise in treatment options for WNBAs.

Novel Use of the Aurora Surgiscope System for Minimally Invasive Resection of Intraparenchymal Lesions: A Case Series.

BACKGROUND: Minimally invasive surgery (MIS) for intracranial pathology minimizes surgical morbidity but can come at the cost of operator ergonomics and technical surgical success. Here, the authors present a case series to report the first use of a novel 15-mm tubular retraction system with integrated lighting and visualization capabilities for MIS access to intracranial lesions. OBJECTIVE: To demonstrate feasibility and effectiveness of the 15-mm Aurora Surgiscope (Integra Lifesciences) for intracranial MIS approaches. METHODS: The 15-mm Aurora Surgiscope facilitated MIS approach to gain access to intraparenchymal pathologies. The device consists of a tubular access system with integrated light source and a reusable control unit that modifies video parameters. The port was inserted along a preplanned trajectory through a mini-craniotomy. Bimanual access allowed the surgeon to comfortably dissect/resect lesional tissue using high-quality video. RESULTS: Four patients are presented. In cases 1 and 2, the authors evacuated acute intracerebral hemorrhages. Both had <15 cc hemorrhage with improved or stable neurological examination. In case 3, the authors performed gross total resection of a cerebellar pilocytic astrocytoma. In case 4, the authors resected a mesial posterior temporal cavernoma. No perioperative/technical complications were noted. CONCLUSION: The Aurora Surgiscope system is a novel integrated tubular retraction, lighting, and visualization system that allows access to a wide variety of pathologies using a MIS approach. The Surgiscope allows the surgeon to use bimanual dexterity through a small access port while limiting the need for additional equipment such as microscope, exoscope, or endoscope.

Endovascular Management of Arteriovenous Malformation-Associated Intracranial Aneurysms: A Systematic Literature Review.

OBJECTIVE: Intracranial aneurysms are present in up to 18% of arteriovenous malformations (AVMs) and increase the risk of intracranial hemorrhage. No consensus exists on the optimal treatment strategy for AVM-associated aneurysms. The goal of this study was to systematically review endovascular treatment methods of AVM-associated intracranial aneurysms, radiographic outcomes, and periprocedural complications. METHODS: A systematic review was performed in accordance with PRISMA guidelines to identify studies that investigated the use of endovascular treatments for management of patients with AVM-associated aneurysms. Collected variables included aneurysm and AVM location, aneurysm size and characteristics, AVM and aneurysm treatment modality, periprocedural complications, and long-term clinical and radiographic outcomes. RESULTS: Eight studies with 237 patients and 314 AVM-associated intracranial aneurysms were included. Two-hundred and twenty-four aneurysms were flow-related (71.3%), 80 were intranidal (25.5%), and 10 were unrelated (3.2%). Complete occlusion was 56.3% (18/32) for aneurysmal coil embolization and 99% (104/105) for parent vessel sacrifice. Of the 13 aneurysms treated with ethanol sclerotherapy, 8 were successfully obliterated (8/13; 61%) using ethanol sclerotherapy alone and the rest required adjunct endovascular embolization for obliteration of the artery and associated aneurysm. The periprocedural complication rate was approximately 12% and consisted of ischemic symptoms, intracranial hemorrhage, and coiling complications. CONCLUSIONS: Endovascular management options of AVM-associated intracranial aneurysms are limited and mostly comprised primary aneurysmal coil embolization or parent vessel sacrifice using coils or liquid embolics. Embolization strategy depends on factors such as AVM angioarchitecture, rupture status, and adjunct AVM treatments.

Use of Surpass Streamline Flow Diverter for the Endovascular Treatment of Craniocervical Aneurysms: A Single-Institution Experience.

BACKGROUND: Flow diversion has revolutionized endovascular treatment for cerebral aneurysms. The Surpass Streamline flow diverter (SSFD) has shown promise for expanding flow diversion device options for aneurysm treatment. SSFD differs from earlier stents by maintaining high porosity with increased pore density to ensure appropriate flow disruption. Given the delivery system's increased dimension options and potential greater flow-diverting properties, SSFD is poised to extend the anatomic and pathologic reaches of flow diversion therapy. METHODS: Data pertaining to SSFD-treated aneurysms were gathered retrospectively between 2019 and 2020, including aneurysm location, size, symptoms, complications, and occlusions rates at follow-up. Size was categorized as small (<10 mm), large (10-25 mm), and giant (>25 mm) according to SCENT (Surpass Intracranial Aneurysm Embolization System Pivotal Trial to Treat Large or Giant Wide Neck Aneurysms) criteria. Aneurysm occlusion on follow-up imaging was characterized by Simple Measurement of Aneurysm Residual after Treatment (SMART) grading with adequate occlusion defined as grades 3 and 4. Imaging was performed at time of treatment and 6-month and 1-year follow-up. RESULTS: There were 42 aneurysms treated with SSFD throughout the cerebrovascular system: 3 cervical, 4 posterior, and 35 intracranial anterior circulation. Complete occlusion rates at 6 months and 1 year were 48% and 57% with adequate occlusion achieved in 89.6% and 85.7%, respectively. Rates of complete occlusion were higher for small (69%) compared with large (38%) aneurysms. CONCLUSIONS: Our data suggest comparable complete occlusion rates compared with SCENT (66.1% vs. 57% in our center) and adequate occlusion rates. Similar occlusion rates to prior studies despite broadened inclusion criteria and diversity of treated aneurysms demonstrate favorable generalizability of flow-diverting technology to a wide array of aneurysmal pathology.

Directed remodeling of the mouse gut microbiome inhibits the development of atherosclerosis.

The gut microbiome is a malleable microbial community that can remodel in response to various factors, including diet, and contribute to the development of several chronic diseases, including atherosclerosis. We devised an in vitro screening protocol of the mouse gut microbiome to discover molecules that can selectively modify bacterial growth. This approach was used to identify cyclic D,L-α-peptides that remodeled the Western diet (WD) gut microbiome toward the low-fat-diet microbiome state. Daily oral administration of the peptides in WD-fed LDLr-/- mice reduced plasma total cholesterol levels and atherosclerotic plaques. Depletion of the microbiome with antibiotics abrogated these effects. Peptide treatment reprogrammed the microbiome transcriptome, suppressed the production of pro-inflammatory cytokines (including interleukin-6, tumor necrosis factor-α and interleukin-1ß), rebalanced levels of short-chain fatty acids and bile acids, improved gut barrier integrity and increased intestinal T regulatory cells. Directed chemical manipulation provides an additional tool for deciphering the chemical biology of the gut microbiome and might advance microbiome-targeted therapeutics.