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.

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.

Neurological Outcomes Following Craniotomy for ECMO-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 2008-2023. Anticoagulation status, operative indication, surgical details, post-operative 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 (mRS 3 at one year). The surviving patient had a notably higher GCS (7T vs 3T), had not received anticoagulation at the time of surgery, and did not experience post-operative re-accumulation or expansion of their hemorrhage, distinguishing factors from the other three included. Review of the existing literature identified 15 adult patients who underwent craniotomy while receiving ECMO therapy, of which four (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.

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.

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.

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.

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.