Nanoliposomes Reduce Stroke Injury Following Middle Cerebral Artery Occlusion in Mice.

BACKGROUND AND PURPOSE: Neuroprotective strategies for stroke remain inadequate. Nanoliposomes comprised of phosphatidylcholine, cholesterol, and monosialogangliosides (nanoliposomes) induced an antioxidant protective response in endothelial cells exposed to amyloid insults. We tested the hypotheses that nanoliposomes will preserve human neuroblastoma (SH-SY5Y) and human brain microvascular endothelial cells viability following oxygen-glucose deprivation (OGD)-reoxygenation and will reduce injury in mice following middle cerebral artery occlusion. METHODS: SH-SY5Y and human brain microvascular endothelial cells were exposed to oxygen-glucose deprivation-reoxygenation (3 hours 0.5%-1% oxygen and glucose-free media followed by 20-hour ambient air/regular media) without or with nanoliposomes (300 µg/mL). Viability was measured (calcein-acetoxymethyl fluorescence) and protein expression of antioxidant proteins HO-1 (heme oxygenase-1), NQO1 (NAD[P]H quinone dehydrogenase 1), and SOD1 (superoxide dismutase 1) were measured by Western blot. C57BL/6J mice were treated with saline (n=8) or nanoliposomes (10 mg/mL lipid, 200 µL, n=7) while undergoing 60-minute middle cerebral artery occlusion followed by reperfusion. Day 2 postinjury neurological impairment score and infarction size were compared. RESULTS: SH-SY5Y and human brain microvascular endothelial cells showed reduced viability post-oxygen-glucose deprivation-reoxygenation that was reversed by nanoliposomes. Nanoliposomes increased protein expressions of HO-1, NQO1 in both cell types and SOD1 in human brain microvascular endothelial cells. Nanoliposomes-treated mice showed reduced neurological impairment and brain infarct size (18.8±2% versus 27.3±2.3%, P=0.017) versus controls. CONCLUSIONS: Nanoliposomes reduced stroke injury in mice subjected to middle cerebral artery occlusion likely through induction of an antioxidant protective response. Nanoliposome is a candidate novel agent for stroke.

Onyx embolization of skull base paragangliomas: a single-center experience.

BACKGROUND: Skull base paragangliomas are highly vascular tumors that are often embolized before surgical resection; however, the safety and efficacy of preoperative embolization using an ethylene vinyl alcohol copolymer (Onyx; Medtronic, Dublin, Republic of Ireland) in these tumors is unknown. This retrospective cohort study evaluated patient outcomes after preoperative embolization of skull base paragangliomas using Onyx. METHODS: We retrospectively analyzed data from all patients with skull base paragangliomas who underwent preoperative Onyx embolization at our institution (January 01, 2005-December 31, 2017). Patient, tumor, embolization, and outcomes data were extracted by reviewing inpatient and outpatient clinical and imaging records. RESULTS: Seven patients were studied (5/7 [71%] female), 6 with glomus jugulares and 1 with a glomus vagale. The median age was 52 years, and the most common presenting symptom was cranial neuropathy (6/7 [86%]). The tumor vascular supply was from the ascending pharyngeal artery in all 7 cases (100%) with additional feeders including the occipital artery in 5 (71%); internal carotid artery in 3 (43%); middle meningeal, vertebral, and internal maxillary artery each in 2 (29%); and posterior auricular artery in 1 (14%). The median postembolization tumor devascularization was 80% (range, 64-95%). The only postembolization complication was a facial palsy in 1 patient. CONCLUSION: Preoperative embolization with Onyx affords excellent devascularization for the majority of skull base paragangliomas, and it may facilitate resection of these hypervascular lesions. The advantages provided by Onyx with respect to penetration of intratumoral vessels must be weighed against the risk of cranial neuropathy.

Middle meningeal artery embolization for chronic subdural hematoma: an institutional technical analysis.

BACKGROUND: Recently, middle meningeal artery (MMA) embolization has emerged as a potentially safe and effective method of treating chronic subdural hematoma (cSDH). OBJECTIVE: To report a single-center experience with MMA embolization and examines the type of embolic material used, the extent of penetration, and the number of MMA branches embolized. METHODS: A retrospective analysis of all patients with MMA embolization from 2018 through 2019 was performed. A failed outcome was defined as either surgical rescue and/or greater than 10 mm of hematoma residual or reaccumulation following embolization. RESULTS: Of 35 patients, surgery had failed for 9 (26%) and initial conservative treatment had failed for 6 (17%). Of 41 MMA embolizations, including those in six patients with bilateral cSDH who underwent bilateral MMA embolization, 29 (72%) were performed using ethylene vinyl alcohol copolymer (Onyx), 7 (17%) using particles, and 5 (12%) using n-butyl cyanoacrylate. Both the anterior and posterior MMA divisions were embolized in 29 cases (71%); distal penetration of these branches was achieved in 25 embolizations (61%). Twenty-six (63%) cSDHs completely resolved. Complete resolution was seen in 22 of 29 hematomas (76%) in which both anterior and posterior MMA branches were occluded versus 4 of 12 (33%) following single-branch embolization (p=0.014). Embolization of one cSDH (2%) failed. CONCLUSION: MMA embolization of cSDHs appears to be both safe and efficacious. Furthermore, embolization of both the anterior and posterior MMA branches may be associated with increased odds of complete resolution.

Preoperative embolization versus no embolization for WHO grade I intracranial meningioma: a retrospective matched cohort study.

OBJECTIVE: The controversy continues over the clinical utility of preoperative embolization for reducing tumor vascularity of intracranial meningiomas prior to resection. Previous studies comparing embolization and nonembolization patients have not controlled for detailed tumor parameters before assessing outcomes. METHODS: The authors reviewed the cases of all patients who underwent resection of a WHO grade I intracranial meningioma at their institution from 2008 to 2016. Propensity score matching was used to generate embolization and nonembolization cohorts of 52 patients each, and a retrospective review of clinical and radiological outcomes was performed. RESULTS: In total, 52 consecutive patients who underwent embolization (mean follow-up 34.8 ± 31.5 months) were compared to 52 patients who did not undergo embolization (mean follow-up 32.8 ± 28.7 months; p = 0.63). Variables controlled for included patient age (p = 0.82), tumor laterality (p > 0.99), tumor location (p > 0.99), tumor diameter (p = 0.07), tumor invasion into a major dural sinus (p > 0.99), and tumor encasement around the internal carotid artery or middle cerebral artery (p > 0.99). The embolization and nonembolization cohorts did not differ in terms of estimated blood loss during surgery (660.4 ± 637.1 ml vs 509.2 ± 422.0 ml; p = 0.17), Simpson grade IV resection (32.7% vs 25.0%; p = 0.39), perioperative procedural complications (26.9% vs 19.2%; p = 0.35), development of permanent new neurological deficits (5.8% vs 7.7%; p = 0.70), or favorable modified Rankin Scale (mRS) score (a score of 0-2) at last follow-up (96.0% vs 92.3%; p = 0.43), respectively. When comparing the final mRS score to the preoperative mRS score, patients in the embolization group were more likely than patients in the nonembolization group to have an improvement in mRS score (50.0% vs 28.8%; p = 0.03). CONCLUSIONS: After controlling for patient age, tumor size, tumor laterality, tumor location, tumor invasion into a major dural sinus, and tumor encasement of the internal carotid artery or middle cerebral artery, preoperative meningioma embolization intended to decrease tumor vascularity did not improve the surgical outcomes of patients with WHO grade I intracranial meningiomas, but it did lead to a greater chance of clinical improvement compared to patients not treated with embolization.

Endovascular occlusion of a ruptured transitional aneurysm associated with a developmental venous anomaly. Case report.

Developmental venous anomalies (DVAs) represent a rare cause of intraparenchymal hemorrhage. This case demonstrates an unusual DVA associated with venous hypertension, arteriovenous shunting, and a ruptured transitional aneurysm. The authors describe the first use of embolization as a treatment method for an unstable ruptured transitional aneurysm associated with a DVA. This 33-year-old man suffered acute onset of headache, gait ataxia, and left hemiparesis. Computed tomography brain scans demonstrated a deep paramedian right frontal intraparenchymal hemorrhage. No cavernous malformation was apparent on MR imaging. Diagnostic angiography revealed arteriovenous shunting from the right anterior and middle cerebral arteries to a large DVA with an associated arteriovenous fistula, with a 3-mm aneurysm in the transition from pericallosal artery to the collecting vein. Both surgical and endovascular treatment options were considered. The patient underwent repeat angiography on hospital Day 7, at which time the aneurysm had increased to 5 mm, and endovascular treatment was selected. Acrylic occlusion of the aneurysm was performed and confirmed angiographically. The patient's neurological symptoms resolved throughout the hospital stay, and he remains symptom free in the 10 months since treatment. Developmental venous anomalies are not usually associated with arteriovenous shunting and aneurysms as a source of intraparenchymal hemorrhage. Endovascular occlusion of the aneurysm without blockage of physiologically necessary venous structures is a possible method of treatment for this complex mixed vascular lesion, and has proven safe and effective in this patient. To the authors' knowledge, this is the first presentation of this situation in the literature.

Use of the Apollo detachable-tip microcatheter for endovascular embolization of arteriovenous malformations and arteriovenous fistulas.

OBJECTIVE: Liquid embolic agents have revolutionized endovascular management of arteriovenous malformations (AVMs) and arteriovenous fistulas (AVFs). Nonetheless, since 2005, the US FDA has received more than 100 reports of microcatheter breakage or entrapment related to Onyx embolization, including 9 deaths. In 2014, the Apollo detachable-tip microcatheter became the first of its kind available in the US. Since then, few reports on its safety have been published. METHODS: The authors conducted a retrospective review of endovascular cases by searching the patient databases at 2 tertiary cerebrovascular centers (Barrow Neurological Institute and University of Pittsburgh Medical Center). Patients who underwent endovascular embolization of an AVM or AVF using the Apollo microcatheter were identified. Patient demographics and lesion characteristics were collected. The authors analyzed Apollo-specific endovascular variables, such as number of microcatheterizations, sessions, and pedicles embolized; microcatheter tip detachment status; obliteration rate; and endovascular- and microcatheter-related morbidity and mortality. RESULTS: From July 2014 to October 2016, a total of 177 embolizations using the Apollo microcatheter were performed in 61 patients (mean age 40.3 years). The most frequent presentation was hemorrhage (22/61, 36.1%). Most lesions were AVMs (51/61, 83.6%; mean diameter 30.6 mm). The mean Spetzler-Martin grade was 2.4. Thirty-nine (76.5%) of 51 patients with AVMs underwent resection. Microcatheterization was successful in 172 pedicles. Most patients (50/61, 82%) underwent a single embolization session. The mean number of pedicles per session was 2.5 (range 1-7). Onyx-18 was used in 103 (59.9%), N-butyl cyanoacrylate (NBCA) in 44 (25.6%), and Onyx-34 in 25 (14.5%) of the 172 embolizations. In 45.9% (28/61) of the patients, lesion obliteration of 75% or greater was achieved. Tip detachment occurred in 19.2% (33/172) of microcatheters. Fifty-three (86.9%) of the 61 patients who underwent embolization with the Apollo microcatheter had good functional outcomes (modified Rankin Scale score 0-2). No unintended microcatheter fractures or related morbidity was observed. One patient died of intraprocedural complications unrelated to microcatheter selection. In the univariate analysis, microcatheter tip detachment (p = 0.12), single embolized pedicles (p = 0.12), and smaller AVM nidus diameter (p = 0.17) correlated positively with high obliteration rates (> 90%). In the multivariate analysis, microcatheter tip detachment was the only independent variable associated with high obliteration rates (OR 9.5; p = 0.03). CONCLUSIONS: The use of the Apollo detachable-tip microcatheter for embolization of AVMs and AVFs is associated with high rates of successful catheterization and obliteration and low rates of morbidity and mortality. The microcatheter was retrieved in all cases, even after prolonged injections in distal branch pedicles, often with significant reflux. This study represents the largest case series on the application of the Apollo microcatheter for neurointerventional procedures.

Preoperative Embolization of Skull Base Meningiomas: Outcomes in the Onyx Era.

OBJECTIVE: Preoperative embolization may facilitate skull base meningioma resection, but its safety and efficacy in the Onyx era have not been investigated. In this retrospective cohort study, we evaluated the outcomes of preoperative embolization of skull base meningiomas using Onyx as the primary embolysate. METHODS: We queried an endovascular database for patients with skull base meningiomas who underwent preoperative embolization at our institution in 2007-2017. Patient, tumor, procedure, and outcome data were analyzed. RESULTS: Twenty-eight patients (28 meningiomas) underwent successful preoperative meningioma embolization. The mean patient age ± SD was 56 ± 13 years, and 18 patients (64%) were women. The mean tumor size was 49 cm3. There were 1, 2, or 3 arterial pedicles embolized in 21 cases (75%), 6 cases (21%), and 1 case (4%), respectively. The embolized pedicles included branches of the middle meningeal artery in 19 cases (68%), the internal maxillary artery in 8 cases (29%), the ascending pharyngeal artery in 2 cases (7%), and the posterior auricular, ophthalmic, occipital, and anterior cerebral arteries in 1 case each (4%). The embolysates used were Onyx alone in 20 cases (71%), n-butyl cyanoacrylate alone in 3 cases (11%), coils/particles and Onyx/n-butyl cyanoacrylate in 2 cases each (7%), and Onyx and coils in 1 case (4%). The median degree of tumor devascularization was 60%. Significant neurologic morbidity occurred in 1 patient (4%) who developed symptomatic peritumoral edema after Onyx embolization. CONCLUSIONS: For appropriately selected skull base meningiomas supplied by dura mater-based arterial pedicles without distal cranial nerve supply, preoperative embolization with current embolysate technology affords substantial tumor devascularization with a low complication rate.

Development of syndrome of inappropriate antidiuretic hormone secretion (SIADH) after Onyx embolisation of a cavernous carotid fistula.

Patients with cavernous carotid fistulas (CCFs) can present with pituitary hypoperfusion and hypopituitarism; however, there are no previous reports of pituitary or hormonal abnormalities developing after CCF embolisation in an asymptomatic patient. We describe a patient with no hormonal abnormalities who developed syndrome of inappropriate antidiuretic hormone (SIADH) secretion after CCF embolisation. The patient had bilateral indirect CCFs, which were completely embolised via a transvenous approach, and was neurologically stable postoperatively and discharged. In the subsequent 2 weeks the patient was readmitted twice for acute hyponatraemia and a tonic-clonic seizure. Laboratory studies revealed severe SIADH. Clinical status and sodium levels improved after treatment. One year later the patient was weaned off all medications and remained neurologically stable. SIADH may be a delayed phenomenon after CCF embolisation. Given the proximity of embolised vessels to the pituitary's vascular supply, CCF treatment may result in flow disturbance, ischaemia and hormonal abnormalities.

Development of syndrome of inappropriate antidiuretic hormone secretion (SIADH) after Onyx embolisation of a cavernous carotid fistula.

Patients with cavernous carotid fistulas (CCFs) can present with pituitary hypoperfusion and hypopituitarism; however, there are no previous reports of pituitary or hormonal abnormalities developing after CCF embolisation in an asymptomatic patient. We describe a patient with no hormonal abnormalities who developed syndrome of inappropriate antidiuretic hormone (SIADH) secretion after CCF embolisation. The patient had bilateral indirect CCFs, which were completely embolised via a transvenous approach, and was neurologically stable postoperatively and discharged. In the subsequent 2 weeks the patient was readmitted twice for acute hyponatraemia and a tonic-clonic seizure. Laboratory studies revealed severe SIADH. Clinical status and sodium levels improved after treatment. One year later the patient was weaned off all medications and remained neurologically stable. SIADH may be a delayed phenomenon after CCF embolisation. Given the proximity of embolised vessels to the pituitary's vascular supply, CCF treatment may result in flow disturbance, ischaemia and hormonal abnormalities.

Neurological morbidity and mortality associated with the endovascular treatment of cerebral arteriovenous malformations before and during the Onyx era.

OBJECT: The widespread implementation of the embolic agent Onyx has changed the endovascular management of cerebral arteriovenous malformations (AVMs). Recent data suggest that outcomes following embolization and resection may have worsened in the Onyx era. It has been hypothesized that there may be increased complications with Onyx embolization and increased surgical aggressiveness in patients treated with Onyx. In this study the authors analyzed their institutional experience with the endovascular treatment of cerebral AVMs prior to and after the introduction of Onyx to determine factors associated with periprocedural neurological morbidity and mortality. METHODS: A retrospective review was performed of all patients with cerebral AVMs undergoing embolization at the Barrow Neurological Institute from 1995 to 2012. RESULTS: Endovascular treatment of 342 cerebral AVMs was performed over 446 treatment sessions (mean age 37.8 years, range 1-83 years). Clinical presentation included hemorrhage in 47.6%, seizures in 21.9%, headaches in 11.1%, and no symptoms in 10% of cases. The endovascular pretreatment strategy was preoperative in 78.9%, preradiosurgery in 9.1%, palliative in 5.3%, targeted in 4.4%, and curative in 2.3%. The median Spetzler-Martin grade was III. The mean number of arteries embolized was 3.5 (range 0-13 arteries), and the mean number of treatment sessions was 1.3 (range 1-4 sessions). Onyx was used in 105 AVMs (30.7%), and N-butyl cyanoacrylate (NBCA) without Onyx was used in 229 AVMs (67%). AVMs treated with Onyx had a higher mean number of arterial pedicles embolized than did NBCA cases (4.3 ± 2.7 vs 3.2 ± 2.4, respectively; p < 0.001) and a greater number of sessions (1.5 ± 0.7 vs 1.2 ± 0.5, respectively; p < 0.05). Unexpected immediate postprocedural permanent neurological deficits were present in 9.6% of AVMs, while transient deficits were present in 1.8%. There was 1 death (0.3%). Spetzler-Martin grade was not associated with differences in outcome, as permanent neurological deficits were observed in 12%, 9%, 13%, 11%, and 13% of AVMs for Spetzler-Martin Grades I-V, respectively (p = 0.91). The use of Onyx compared with NBCA was not associated with differences in periprocedural morbidity (p = 0.23). This lack of a difference persisted even when controlling for number of arteries and sessions (p = 0.14). Sex was not associated with differences in outcome. CONCLUSIONS: Permanent and transient postprocedural neurological deficits were noted in 9.6% and 1.8% of all cases, respectively. AVM grade was not associated with endovascular outcome. Despite the greater number of sessions required and arteries embolized for Onyx cases, there was no statistically significant difference in the risk of neurological deficits following cerebral AVM embolization with Onyx and NBCA.

Complex dural arteriovenous fistula in Bannayan-Riley-Ruvalcaba syndrome.

In this paper the authors report the case of a complex dural arteriovenous fistula (dAVF) with high-risk features in a 14-year-old girl with Bannayan-Riley-Ruvalcaba syndrome (BRRS), a phosphatase and tensin homolog-associated syndrome, presenting with signs and symptoms of increased intracranial pressure (ICP) that had previously been attributed to pseudotumor cerebri. This fistula was obliterated following 2 stages of embolization, and the patient experienced immediate symptomatic improvement. At the 2-month follow-up evaluation, the fistula remained angiographically occluded, and her symptoms continue to improve. This is the third reported case of an intracranial dAVF in a patient with BRRS. Because high-risk dAVFs can result in devastating morbidity, early detection with vascular imaging is crucial for patients with BRRS presenting with signs of increased ICP. Goals of treatment should include complete fistula obliteration whenever possible.