Middle meningeal artery embolization reduces recurrence following surgery for septated chronic subdural hematomas.

BACKGROUND: Septated chronic subdural hematomas (cSDH) have high rates of recurrence despite surgical evacuation. Middle meningeal artery embolization (MMAE) has emerged as a promising adjuvant for secondary prevention, yet its efficacy remains ill-defined. METHODS: This is a retrospective review of septated cSDH cases treated at our institution. The surgery-only group was derived from cases performed before 2018, and the surgery+MMAE group was derived from cases performed 2018 or later. The primary outcome was reoperation rate. Secondary outcomes were recurrence, change in hematoma thickness, and midline shift. RESULTS: A total of 34 cSDHs in 28 patients (surgery+MMAE) and 95 cSDHs in 83 patients (surgery-only) met the inclusion criteria. No significant difference in baseline characteristics between groups was identified. The reoperation rate was significantly higher in the surgery-only group (n = 16, 16.8%) compared with the surgery+MMAE cohort (n = 0, 0.0%) (p=0.006). A reduced incidence of recurrence (p=0.011) was also seen in the surgery+MMAE group. CONCLUSIONS: MMAE for septated cSDH was found to be highly effective in preventing recurrence and reoperation. MMAE is an adjunct to surgical evacuation may be of particular benefit in this patient cohort.

Angiographic characteristics and treatment approach in patients undergoing intra-arterial chemotherapy for retinoblastoma.

PURPOSE: To identify the specific clinical and angiographic variables that determine the success of intra-arterial chemotherapy (IAC) in a patient with retinoblastoma. METHODS: Medical records from patients undergoing intra-arterial chemotherapy for the treatment of retinoblastoma between January 2015 and June 2020 within a large academic ocular oncology practice were retrospectively reviewed. Demographics were recorded together with clinical, ocular, and angiographic variables such as the diameter of the ophthalmic artery (OA), angle of ophthalmic artery takeoff, and branching pattern of ophthalmic vasculature. RESULTS: Forty-four eyes from 33 patients with retinoblastoma treated with IAC were identified. Over the total 32 mean months of follow-up, these patients received 144 total catheterizations and a mean of 3.2 IAC cycles for each eye. The number of IAC cycles and the chemotherapeutic agent used did not vary significantly with worsening International Classification of Retinoblastoma (ICRB) groups (P > 0.1). Cumulative dose did not vary with the ICRB group for eyes treated with melphalan, topotecan, or carboplatin (P > 0.1). A higher ICRB group was associated with a smaller mean ophthalmic artery diameter across all procedures (P = 0.016), and femoral artery diameter did not vary significantly between ICRB groups (P = 0.906). A higher cumulative dose of IAC was significantly associated with a smaller takeoff angle of the OA (melphalan, P = 0.011; topotecan, P = 0.009; carboplatin, P = 0.031) in patients who underwent successful IAC procedures. Ophthalmic artery diameter and femoral artery diameter did not have a significant association (P > 0.1) with higher IAC doses in successful IACs. Cumulative IAC dose was not significantly associated with ophthalmic vasculature branching pattern, presence of choroidal blush, temporary OA vasospasm reported during the procedure, and OA occlusion upon microcatheter placement. CONCLUSION: In this study, neurosurgical angioanatomy appeared to influence the cumulative dose of chemotherapy needed during IAC for retinoblastoma. In the future, these anatomic variables may be used to guide the frequency of monitoring, dosing, and estimation of recurrence risk.

Incidence and Risk Factors for Neutropenia After Intra-Arterial Chemotherapy for Retinoblastoma.

Importance: Intra-arterial chemotherapy (IAC) has quickly gained popularity as a mainstay of treatment for retinoblastoma. Intra-arterial chemotherapy has been described as having several advantages over systemic chemotherapy, including reducing systemic toxicity and neutropenia; however, studies on the risk of neutropenia after IAC remain limited. Objective: To estimate the incidence of neutropenia after IAC, as well as identify risk factors associated with the development of neutropenia. Design, Setting, and Participants: This case series included pediatric patients with unilateral or bilateral retinoblastoma who were treated with IAC at a single quaternary care center from July 13, 2013, to January 6, 2023. Exposure: All patients were treated with IAC and underwent multiple IAC cycles depending on treatment response. The primary chemotherapy agent used was melphalan, but topotecan or carboplatin could be used along with melphalan. Melphalan doses were kept to 0.4 mg/kg or less per cycle. After each IAC cycle, complete blood cell counts were obtained within 10 to 12 days and repeated until the absolute neutrophil count (ANC) was greater than or equal to 1000/µL. Main Outcomes and Measures: The primary outcome was the minimum ANC after each IAC cycle. The secondary outcome was the development of severe (grade 3 or 4) neutropenia (ANC <1000/µL). Regression analyses were used to identify associations between variables and outcomes. Receiver operating characteristic curves were used to calculate threshold dose for each chemotherapy agent potentially associated with the development of severe neutropenia. Results: A total of 64 eyes of 49 patients (mean [SD] age, 1.7 [1.2] years; 25 females [51.0%]) with retinoblastoma were treated with 171 cycles of IAC. The mean (SD) nadir ANC was 1325.3 (890.7)/µL and occurred a median (IQR) of 10 (10-14) days (range, 6-28 days) after IAC administration. The frequency distribution of post-IAC neutropenia grades 0, 1, 2, 3, 4, and missing was 31 (18.1% of cycles), 25 (14.6%), 40 (23.4%), 37 (21.6%), 26 (15.2%), and 12 (7.0%), respectively. Factors weakly correlated with a lower ANC were higher melphalan dose (ß = -2356 [95% CI, -4120.6 to -611.2]; adjusted R2 = 0.251; P = .01) and higher topotecan dose (ß = -4056 [95% CI, -7003.6 to -1344.5]; adjusted R2 = 0.251; P = .006). Conclusions and Relevance: In this case series of patients with retinoblastoma, the incidence of severe neutropenia after IAC was nearly 40%, which is higher than previously reported. Extended laboratory monitoring may aid in capturing previously overlooked cases of neutropenia. Topotecan may be associated with the development of neutropenia; limiting topotecan doses, especially in the setting of a high melphalan dose, may be beneficial in reducing the risk of neutropenia.

Middle meningeal artery embolization of septated chronic subdural hematomas.

INTRODUCTION: Middle meningeal artery embolization (MMAE) has emerged as a promising new treatment for patients with chronic subdural hematomas (cSDH). Its efficacy, however, upon the subtype with a high rate of recurrence-septated cSDH-remains undetermined. METHODS: From our prospective registry of patients with cSDH treated with MMAE, we classified patients based on the presence or absence of septations. The primary outcome was the rate of recurrence of cSDH. Secondary outcomes included a reduction in cSDH thickness, midline shift, and rate of reoperation. RESULTS: Among 80 patients with 99 cSDHs, the median age was 68 years (IQR 59-77) with 20% females. Twenty-eight cSDHs (35%) had septations identified on imaging. Surgical evacuation with burr holes was performed in 45% and craniotomy in 18.8%. Baseline characteristics between no-septations (no-SEP) and septations (SEP) groups were similar except for median age (SEP vs no-SEP, 72.5 vs. 65.5, p = 0.016). The recurrence rate was lower in the SEP group (SEP vs. no-SEP, 3 vs. 16.7%, p = 0.017) with higher odds of response from MMAE for septated lesions even when controlling for evacuation strategy and antithrombotic use (OR = 0.06, CI [0.006-0.536], p = 0.012). MMAE resulted in higher mean absolute thickness reduction (SEP vs. no-SEP, -8.2 vs. -4.8 mm, p = 0.016) with a similar midline shift change. The rate of reoperation did not differ (6.2 vs. 3.1%, p = 0.65). CONCLUSION: MMAE appears to be equal to potentially more effective in preventing the recurrence of cSDH in septated lesions. These findings may aid in patient selection.

Middle Meningeal Artery Embolization for Chronic Subdural Hematomas With Concurrent Antithrombotics.

BACKGROUND: Chronic subdural hematoma (CSDH) is an increasingly prevalent disease in the aging population. Patients with CSDH frequently suffer from concurrent vascular disease or develop secondary thrombotic complications requiring antithrombotic treatment. OBJECTIVE: To determine the safety and impact of early reinitiation of antithrombotics after middle meningeal artery embolization for chronic subdural hematoma. METHODS: This is a single-institution, retrospective study of patients who underwent middle meningeal artery (MMA) embolizations for CSDH. Patient with or without antithrombotic initiation within 5 days postembolization were compared. Primary outcome was the rate of recurrence within 60 days. Secondary outcomes included rate of reoperation, reduction in CSDH thickness, and midline shift. RESULTS: Fifty-seven patients met inclusion criteria. The median age was 66 years (IQR 58-76) with 21.1% females. Sixty-six embolizations were performed. The median length to follow-up was 20 days (IQR 14-44). Nineteen patients (33.3%) had rapid reinitiation of antithrombotics (5 antiplatelet, 11 anticoagulation, and 3 both). Baseline characteristics between the no antithrombotic (no-AT) and the AT groups were similar. The recurrence rate was higher in the AT group (no-AT vs AT, 9.3 vs 30.4%, P = .03). Mean absolute reduction in CSDH thickness and midline shift was similar between groups. Rate of reoperation did not differ (4.7 vs 8.7%, P = .61). CONCLUSION: Rapid reinitiation of AT after MMA embolization for CSDH leads to higher rates of recurrence with similar rates of reoperation. Care must be taken when initiating antithrombotics after treatment of CSDH with MMA embolization.

Integrated Stroke System Model Expands Availability of Endovascular Therapy While Maintaining Quality Outcomes.

BACKGROUND AND PURPOSE: The optimal endovascular stroke therapy (EVT) care delivery structure is unknown. Here, we present our experience in creating an integrated stroke system (ISS) to expand EVT availability throughout our region while maintaining hospital and physician quality standards. METHODS: We identified all consecutive patients with large vessel occlusion acute ischemic stroke treated with EVT from January 2014 to February 2019 in our health care system. In October 2017, we implemented the ISS, in which 3 additional hospitals (4 total) became EVT-performing hospitals (EPHs) and physicians were rotated between all centers. The cohort was divided by time into pre-ISS and post-ISS, and the primary outcome was time from stroke onset to EPH arrival. Secondary outcomes included hospital and procedural quality metrics. We performed an external validation using data from the Southeast Texas Regional Advisory Council. RESULTS: Among 513 patients with large vessel occlusion acute ischemic stroke treated with EVT, 58% were treated pre-ISS and 43% post-ISS. Over the study period, EVT procedural volume increased overall but remained relatively low at the 3 new EPHs (<70 EVT/y). After ISS, the proportion of patients who underwent interhospital transfer decreased (46% versus 37%; P<0.05). In adjusted quantile regression, ISS implementation resulted in a reduction of time from stroke onset to EPH arrival by 40 minutes (P<0.01) and onset to groin puncture by 29 minutes (P<0.05). Rates of postprocedural hemorrhage, modified Thrombolysis in Cerebral Infarction (TICI) 2b/3, and 90-day modified Rankin Scale were comparable at the higher and lower volume EPHs. The improvement in onset-to-arrival time was not reflective of overall improvement in secular trends in regional prehospital care. CONCLUSIONS: In our system, increasing EVT availability decreased time from stroke onset to EPH arrival. The ISS provides a framework to maintain quality in lower volume hospitals.

Endovascular thrombectomy in patients with large core ischemic stroke: a cost-effectiveness analysis from the SELECT study.

BACKGROUND: It is unknown whether endovascular thrombectomy (EVT) is cost effective in large ischemic core infarcts. METHODS: In the prospective, multicenter, cohort study of imaging selection study (SELECT), large core was defined as computed tomography (CT) ASPECTS<6 or computed tomography perfusion (CTP) ischemic core volume (rCBF<30%) ≥50 cc. A Markov model estimated costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) of EVT compared with medical management (MM) over lifetime. The willingness to pay (WTP) per QALY was set at $50 000 and $100 000 and the net monetary benefits (NMB) were calculated. Probabilistic sensitivity analysis (PSA) and cost-effectiveness acceptability curves (CEAC) for EVT were assessed in SELECT and other pivotal trials. RESULTS: From 361 patients enrolled in SELECT, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT vs 6 (14%) MM patients achieved modified Rankin Scale (mRS) score 0-2 (OR 3.27, 95% CI 1.11 to 9.62, P=0.03) with a shift towards better mRS (cOR 2.12, 95% CI 1.05 to 4.31, P=0.04). Over the projected lifetime of patients presenting with large core, EVT led to incremental costs of $33 094 and a gain of 1.34 QALYs per patient, resulting in ICER of $24 665 per QALY. EVT has a higher NMB compared with MM at lower (EVT -$42 747, MM -$76 740) and upper (EVT $155 041, MM $57 134) WTP thresholds. PSA confirmed the results and CEAC showed 77% and 92% acceptability of EVT at the WTP of $50 000 and $100 000, respectively. EVT was associated with an increment of $29 225 in societal costs. The pivotal EVT trials (HERMES, DAWN, DEFUSE 3) were dominant in a sensitivity analysis at the same inputs, with societal cost-savings of $37 901, $86 164 and $22 501 and a gain of 1.62, 2.36 and 2.21 QALYs, respectively. CONCLUSIONS: In a non-randomized prospective cohort study, EVT resulted in better outcomes in large core patients with higher QALYs, NMB and high cost-effectiveness acceptability rates at current WTP thresholds. Randomized trials are needed to confirm these results. CLINICAL TRIAL REGISTRATION: NCT02446587.

Impact of Initial Imaging Protocol on Likelihood of Endovascular Stroke Therapy.

BACKGROUND AND PURPOSE: Noncontrast head CT and CT perfusion (CTP) are both used to screen for endovascular stroke therapy (EST), but the impact of imaging strategy on likelihood of EST is undetermined. Here, we examine the influence of CTP utilization on likelihood of EST in patients with large vessel occlusion (LVO). METHODS: We identified patients with acute ischemic stroke at 4 comprehensive stroke centers. All 4 hospitals had 24/7 CTP and EST capability and were covered by a single physician group (Neurology, NeuroIntervention, NeuroICU). All centers performed noncontrast head CT and CT angiography in the initial evaluation. One center also performed CTP routinely with high CTP utilization (CTP-H), and the others performed CTP optionally with lower utilization (CTP-L). Primary outcome was likelihood of EST. Multivariable logistic regression was used to determine whether facility type (CTP-H versus CTP-L) was associated with EST adjusting for age, prestroke mRS, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, LVO location, time window, and intravenous tPA (tissue-type plasminogen activator). RESULTS: Among 3107 patients with acute ischemic stroke, 715 had LVO, of which 403 (56%) presented to CTP-H and 312 (44%) presented to CTP-L. CTP utilization among LVO patients was greater at CTP-H centers (72% versus 18%, CTP-H versus CTP-L, P<0.01). In univariable analysis, EST rates for patients with LVO were similar between CTP-H versus CTP-L (46% versus 49%). In multivariable analysis, patients with LVO were less likely to undergo EST at CTP-H (odds ratio, 0.59 [0.41-0.85]). This finding was maintained in multiple patient subsets including late time window, anterior circulation LVO, and direct presentation patients. Ninety-day functional independence (odds ratio, 1.04 [0.70-1.54]) was not different, nor were rates of post-EST PH-2 hemorrhage (1% versus 1%). CONCLUSIONS: We identified an increased likelihood for undergoing EST in centers with lower CTP utilization, which was not associated with worse clinical outcomes or increased hemorrhage. These findings suggest under-treatment bias with routine CTP.

USE OF FEMORAL ARTERY ULTRASOUND DURING INTRAARTERIAL CHEMOTHERAPY FOR CHILDREN UNDER 10 KG WITH RETINOBLASTOMA.

PURPOSE: To demonstrate the safety and efficacy of intraarterial chemotherapy (IAC) in small infants (<10 kg) with retinoblastoma. METHODS: Retrospective, consecutive, observational case series of patients treated with IAC. Femoral arterial access was obtained using a micropuncture kit and ultrasound guidance, which enabled direct visualization. Melphalan (1.5-5.0 mg), topotecan (0.3-2.0 mg), and/or carboplatin (30-40 mg) were used. Patients underwent adjuvant therapies including laser, cryotherapy, and intravitreal melphalan if persistent disease or recurrence was observed. RESULTS: Fifty-nine injections were administered to 11 eyes of 6 patients. All eyes but one were classified as International Classification Groups C or D. Median patient weight at first IAC cycle was 9.2 kg (mean, 8.9 kg). Median diameter of the femoral artery at the catheterization site was 3.74 mm, measured by two independent observers. Median follow-up was 21.4 months (range 13.1-34.5 months). All eyes were salvaged. CONCLUSION: This study confirmed the safety and efficacy of IAC in infants under 10 kg. Ultrasound guidance enabled successful catheterization of femoral arteries as small as 2.7 mm in diameter. Patients in this study appeared to require fewer injections and lower total doses of chemotherapy compared with previously reported series of comparably advanced disease in larger infants.

Quantification of Cerebral Edema After Subarachnoid Hemorrhage.

BACKGROUND: Global cerebral edema (GCE) is a manifestation of early brain injury (EBI) after subarachnoid hemorrhage (SAH) and is an independent risk factor for poor outcome. The lack of a quantitative method to measure GCE limits the study of its pathophysiology. The goal of this study is to develop a quantitative surrogate marker that represents GCE after SAH. METHODS: Patients with spontaneous SAH were enrolled into a prospective observational database. Initial CT scans were graded for GCE using established qualitative criteria. Selective sulcal volume (SSV) was defined as total mL of sulcal volumes on axial CT slices above the most cranial section of the lateral ventricles to the last visible section. Using a semiautomatic threshold approach, sulcal regions were traced out with manual adjustments when necessary. The volume of sulci in each slice was calculated and multiplied by the slice thickness and number of slices to calculate the SSV. All volumetric analysis was performed using Medical Image Processing, Analysis and Visualization Version 7.0.1 (MIPAV). RESULTS: A total of 109 subjects were included in our analysis. Mean selective sulcal volumes (SSV) differed between subjects with and without GCE 4.5 and 21.2 mL (P < 0.001). When separated into quartiles, the odds of qualitative GCE increases as SSV decreases. Compared to the highest SSV quartile, smaller SSV was associated with worse clinical outcomes. CONCLUSION: GCE can be quantified using volumetric analysis of SSV measurements on routine CT scans. Smaller SSV on admission is predictive of worse clinical outcomes. SSV may be an important marker of EBI after SAH.

Effect of antiplatelet therapy and platelet function testing on hemorrhagic and thrombotic complications in patients with cerebral aneurysms treated with the pipeline embolization device: a review and meta-analysis.

PURPOSE: The pipeline embolization device (PED) necessitates dual antiplatelet therapy (APT) to decrease thrombotic complications while possibly increasing bleeding risks. The role of APT dose, duration, and response in patients with hemorrhagic and thromboembolic events warrants further analysis. METHODS: A PubMed and Google Scholar search from 2009 to 2014 was performed using the following search terms individually or in combination: pipeline embolization device, aneurysm(s), and flow diversion, excluding other flow diverters. Review of the bibliographies of the retrieved articles yielded 19 single and multicenter studies. A statistical meta-analysis between aspirin (ASA) dose (low dose ≤160 mg, high dose ≥300 mg), loading doses of APT agents, post-PED APT regimens, and platelet function testing (PFT) with hemorrhagic or thrombotic complications was performed. RESULTS: ASA therapy for ≤6 months post-PED was associated with increased hemorrhagic events. High dose ASA ≤6 months post-PED was associated with fewer thrombotic events compared with low dose ASA. Post-PED clopidogrel for ≤6 months demonstrated an increased incidence of symptomatic thrombotic events. Loading doses of ASA plus clopidogrel demonstrated a decreased incidence of permanent symptomatic hemorrhagic events. PFT did not show a statistically significant relationship with symptomatic hemorrhagic or thrombotic complications. CONCLUSIONS: High dose ASA >6 months is associated with fewer permanent thrombotic and hemorrhagic events. Clopidogrel therapy ≤6 months is associated with higher rates of thrombotic events. Loading doses of ASA and clopidogrel were associated with a decreased incidence of hemorrhagic events. PFT did not have any significant association with symptomatic events.

Subarachnoid haemorrhage associated with an intrathecal catheter.

Although 15 to 20 percent of patients with subarachnoid haemorrhage (SAH) do not have a vascular lesion on four-vessel cerebral angiography, venous injury is a potential cause. This case describes an intracranial catheter associated with nonaneurysmal SAH. It suggests that intrathecal catheters can cause vascular injury, and that nonaneurysmal perimesencephalic SAH may be due to injury of small blood vessels.

Indocyanine green videoangiography for confirmation of bypass graft patency.

OBJECTIVE: The aim of the study is to determine the efficacy of indocyanine green (ICG) videoangiography for confirmation of vascular anastomosis patency in both extracranial-intracranial and intracranial-intracranial bypasses. METHODS: Intraoperative ICG videoangiography was used as a surgical adjunct for 56 bypasses in 47 patients to assay the patency of intracranial vascular anastomosis. These patients underwent a bypass for cerebral ischemia in 31 instances and as an adjunct to intracranial aneurysm surgery in 25. After completion of the bypass, ICG was administered to assess the patency of the graft. The findings on ICG videoangiography were then compared to intraoperative and/or postoperative imaging. RESULTS: ICG provided an excellent visualization of all cerebral arteries and grafts at the time of surgery. Four grafts were determined to be suboptimal and were revised at the time of surgery. Findings on ICG videoangiography correlated with intraoperative and/or postoperative imaging. CONCLUSION: ICG videoangiography is rapid, effective, and reliable in determining the intraoperative patency of bypass grafts. It provides intraoperative information allowing revision to reduce the incidence of technical errors that may lead to early graft thrombosis.

Diagnosing cranial fasciitis based on distinguishing radiological features.

Primary skull lesions, albeit rare in the pediatric population, have been well described and classified. These lesions are usually benign and commonly present as a painless mass. The most common lesions are epidermoid, dermoid, and Langerhans cell histiocytosis. Cranial fasciitis, encountered less frequently, is usually not considered in this differential diagnosis. Given such few cases reported, it is commonly misdiagnosed preoperatively. The authors retrospectively reviewed data obtained in 4 patients with cranial fasciitis in whom the diagnosis was based on histopathological findings. In 2 patients the onset of the lesion was spontaneous. One patient had a lesion 4 months following a vacuum extraction and subsequent cephalohematoma formation. One patient developed a lesion following a previous craniectomy. Presentation, imaging studies, and histopathological findings were all reviewed and analyzed. All patients presented with a firm nontender mass. Radiological features included a lytic bone lesion with a mildly sclerotic margin, T1 isodensity, T2 heterogeneous hyperdensity, and heterogeneous enhancement. The enhancing portion was not bright on T2-weighted MR images, likely representing the fibrous component; the nonenhancing portion was bright on T2-weighted images, likely representing the myxoid matrix. Histopathological examination revealed proliferating fibroblasts in a myxoid matrix. Cranial fasciitis is a benign, painless but rapidly growing lesion of the skull mainly limited to the pediatric population. It is histologically similar to nodular fasciitis, a fibroblastic proliferation of varying size. These lesions are often related to trauma but can also be insidious or can develop at a prior craniectomy site. The appropriate clinical picture and distinguishing radiographic features may help to differentiate cranial fasciitis from other lesions of the skull allowing for earlier intervention.