Double Stent-Assisted (Y and X) Coil Embolization of Unruptured Intracranial Saccular Aneurysms using the Low-Profile Visualized Intraluminal Support Device-Single Center Experience.

PURPOSE: To study the feasibility, safety, and durability of the dual stent-assisted coil embolization (DSCE) technique using low-profile visualized intraluminal support (LVIS) device. METHODS: Retrospective review of our aneurysm database to identify all the patients treated with LVIS stent-assisted embolization between July 2015 and June 2017 was performed. 15% of the patients with Y- or X-configuration DSCE constituted the study population. Patient demographics, clinical presentation, aneurysm characteristics (location, dome, and dome/neck ratio), periprocedural complications, immediate and follow-up angiographic and clinical outcomes were reported. RESULTS: Twelve patients (15%) with unruptured, wide-necked branching aneurysms underwent DSCE using LVIS Junior stents. M:F-1:11. Mean age of 60 ± 11 years. 75% (n = 9) aneurysms are located in anterior circulation. Recurrent aneurysms were treated in 17% (n = 2). Mean aneurysm diameter was 8 ± 3.4 mm and the dome/neck ratio was 1.6 ± 0.4. Periprocedural complications were noted in 25% (n = 3; transient in-stent thrombus = 2 and iatrogenic rupture = 1) with no clinical sequelae. Immediate aneurysm obliteration following DSCE was noted in all (100%) patients. Mean time-of-flight (TOF) magnetic resonance angiography (MRA) follow-up was 10 ± 6 months (Range: 5-19 months). Mean clinical follow-up was 12 ± 6 months (Range: 5-21 months). Stable neck recurrence was demonstrated in 25% (n = 3). The average modified Rankin Score (mRS) at prestent, 24-hour poststent, and last clinical follow-up were: 0.5 (Range: 0-1), 0.75 (Range: 0-1), and 0.5 (Range: 0-1), respectively. CONCLUSION: We report the first dedicated DSCE experience with LVIS Junior stents in the literature. DSCE with LVIS Junior stents for intracranial complex wide-neck branching aneurysms is feasible, safe, and effective with good clinical outcomes.

Treatment of Unruptured Brain Arteriovenous Malformations: A Single-Center Experience of 86 Patients and a Critique of the A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) Trial.

OBJECTIVE: The A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) trial has received fierce criticism, including considerable selection bias, poor generalizability, questionable clinical practices (only 15.8% underwent surgical resection, the gold standard for arteriovenous malformation [AVM] treatment), and short follow-up (33 months) for a disease process that carries a life-long risk. In this study, we sought to present our own experience treating unruptured brain AVMs to provide supporting evidence of the ARUBA trial criticism. METHODS: All cases of treated brain AVMs from 2004 to 2017 at our institution were retrospectively reviewed and included in the analysis if they met ARUBA trial inclusion criteria. The primary outcome was symptomatic stroke or death. Secondary outcomes included AVM obliteration, long-term clinical impairment (modified Rankin Scale score >1), and new major or minor postoperative deficit. RESULTS: Of the 245 reviewed cases, 86 met the ARUBA trial criteria. Treatment included microsurgical resection alone (2.3%), preoperative embolization followed by microsurgical resection (62.8%), stereotactic radiosurgery alone (10.5%), embolization followed by stereotactic radiosurgery (15.1%), and embolization alone (9.3%). The primary outcome was met in 8.3%, new perioperative major and minor complications occurred in 5.8% and 12.8%, and long-term clinical impairment in 4.5%. AVM obliteration was observed in 92.4% overall and in 100% of patients who underwent surgical resection. CONCLUSIONS: The criticism of the ARUBA trial is warranted, as our study found that treatment of unruptured brain AVMs has an acceptable safety profile when approached in a multidisciplinary manner at an experienced institution, using surgical resection as the primary treatment modality when applicable.

Anatomic measurements of cerebral venous sinuses in idiopathic intracranial hypertension patients.

PURPOSE: Magnetic resonance venography (MRV) has not been validated in pre-operative planning of the dural venous sinus stenting (VSS) among idiopathic intracranial hypertension (IIH) patients. We aim to prospectively evaluate dural venous sinus measurement in IIH patient population on two-dimensional time-of-flight (2D-TOF) MRV and Three-dimensional contrast-enhanced (3D-CE) MRV acquisitions and compare them against real-time endoluminal measurements with intravascular ultrasound (IVUS), served as the reference. MATERIALS AND METHODS: The study has been approved by the Weill Cornell Medicine institutional review board. All patients signed written informed consent approved by IRB. Prospective evaluation of forty-five consecutive IIH patients treated with VSS at our institution were evaluated. Patients with pre-stent magnetic resonance venography (MRV) ≤ 6-months of VSS and intravascular ultrasound (IVUS) during VSS constituted the study population. Maximum diameter (in mm), Area (in cm2) and Perimeter (in cm) were measured at posterior 1/3rd of superior sagittal sinus (SSS), proximal transverse sinus (PTS), proximal sigmoid sinus (PSS) and mid sigmoid sinus (MSS) on 2D-TOF-MRV, 3D-CE-MRV and IVUS. Statistical analysis performed using box and whisker plots, Bland-Altman analysis and paired sample t-test. RESULTS: Twenty (n = 20) patients constituted our study population. The mean age was 30±11 years (7-59 years) and 18 out of 20 were female patients. Mean weight and BMI (range) were 86.3±18.3 kilograms (30.8-107.5 kgs) and 32.9±6.8 kg/M2 (16.4-48.3kg/M2) respectively. The CE-MRV significantly oversized the cerebral venous sinuses compared to TOF-MRV (Dmax: +2.0±1.35 mm, p<0.001; Area: +13.31±10.92 mm2, p<0.001 and Perimeter: +4.79±3.4 mm, p<0.001) and IVUS (Dmax: +1.52±2.16 mm, p<0.001; Area: +10.03±21.5 mm2, p<0.001 and Perimeter: +4.15±3.27 mm, p<0.001). The TOF-MRV sinus measurements were in good agreement with the IVUS measurements with no significant variation (Dmax: +.21±2.23 mm, p = 0.49; Area: +2.51±20.41mm2, p = 0.347 and Perimeter: +.001±1.11 mm, p = 0.991). CONCLUSION: We report baseline cerebral venous sinus measurements (maximum diameter, area and perimeter) in patients with idiopathic intracranial hypertension. In our experience, TOF-MRV is a reliable representation of endoluminal cerebral venous sinus dimensions, and CE-MRV measurements reflected an overestimation of the endoluminal sinus dimensions when compared against the real time IVUS measurements.

Pressure variations in cerebral venous sinuses of idiopathic intracranial hypertension patients.

PURPOSE: To evaluate the alteration of pressure characteristics in the cerebral venous sinuses before and after venous sinus stenting (VSS) using mean sinus pressures (MSPs), sinus pressure gradient (SPG), and sinus pressure pulsatility (SPP) parameters among the idiopathic intracranial hypertension (IIH) patients. MATERIALS AND METHODS: Prospective evaluation of 45 consecutive IIH patients who underwent VSS at our institution. A written informed consent approved by the Weill Cornell Institutional Review Board was signed by the study participants. All patients (n = 45) were evaluated for MSPs and SPG. In a subgroup of 12 (n = 12) consecutive patients, SPP was measured. MSP was measured using microcatheter at superior sagittal sinus (SSS), transverse sinus (TS), and sigmoid sinus (SS). SPG was measured as trans-stenotic gradient and trans-torcular gradient. SPP was recorded in the dominant TS with a six French intermediate catheter. Statistical analysis was performed using paired student t-test and two sample t-tests tested for both equal and unequal variances. P values below 0.05 were considered significant. RESULTS: The mean age of the study population was 30.6 ± 10 years (7-59 years) and 43 out of 45 are female patients. The mean weight and BMI of the study population were 96 ± 24.7 kg (30.8-144 kg) and 35.6 ± 8.3 kg/M2 (16.4-51.4 kg/M2), respectively. VSS in IIH patients resulted in immediate reduction of MSP in the SSS {Δ Mean: -8.1 mm Hg [95% confidence interval (CI): -5.0-11.7 mm Hg], p < 0.001} and TS [Δ Mean: -11.8 mm Hg (95% CI: -7.5 to 13.4 mm Hg), p < 0.001] and increase of MSP in SS [Δ Mean: 7.5 mm Hg (95% CI: 6-10.1 mm Hg), p < 0.001]. Significant reduction of trans-stenotic SPG reduction [Δ Mean: -15.7 mm Hg (95% CI: -13.6-17.8 mm Hg), p < 0.001] and SPP [Δ Mean: -8 mm Hg (95% CI: -2.5-13.4 mm Hg), p < 0.05] was observed following VSS. CONCLUSION: VSS resulted in immediate alteration of the cerebral venous sinus pressure measurements in patients with IIH.

Contrast enhanced magnetic resonance venography in the follow-up evaluation of idiopathic intracranial hypertension patients with cerebral venous sinus stenting.

PURPOSE: Role of contrast-enhanced magnetic resonance venography (CE-MRV) in the follow-up of venous sinus stenting (VSS) among the idiopathic intracranial hypertension (IIH) patients. MATERIALS AND METHODS: Prospective evaluation of VSS patients with CE-MRV, DRCV and DSA for follow-up of clinically suspected recurrent stenosis. CE-MRV was evaluated against DRCV and DSA. RESULTS: Ten patients with twelve episodes of recurrent symptoms. Sensitivity, specificity, PPV, NPV and accuracy of the CE-MRV for the detection of recurrent stenosis were: 100%, 33.33%, 81.82%, 100% and 83.3% respectively. CONCLUSION: CE-MRV was a reliable first-line investigation for the detection of recurrent stenosis following VSS.

Endovascular treatment of middle cerebral artery aneurysms: A single center experience with a focus on thromboembolic complications.

Background Endovascular treatment of middle cerebral artery (MCA) aneurysms has traditionally been considered difficult due to complex branching patterns, frequent involvement of parent vessels within the aneurysm neck, and a high incidence of thromboembolic complications. Methods The cases of 93 MCA aneurysms treated with endovascular intervention at our institution between 2003 and 2015 were retrospectively reviewed. Demographic, clinical, and radiographic variables were recorded and analyzed. Results Immediate complete or near-complete occlusion was achieved in 81 (90%) cases. At the longest follow up of 6 months or greater, 83.3% of the aneurysms were stable-to-improved in the Raymond occlusion classification, 8.3% were found to have minor recanalization not requiring retreatment, and 8.3% required retreatment due to significant recanalization. Thromboembolic events occurred in 18 (19.3%) of cases, but only 1 resulted in permanent vessel occlusion and only 1 resulted in permanent neurologic impairment. Thrombus was resolved with intra-arterial thrombolysis or mechanical thrombectomy in 17 of the 18 cases. There were only two cases resulting in morbidity (2.15%). There was no statistically significant correlation between aneurysm location, size, morphology, or use of adjuvant device with radiographic outcome or thromboembolic event. Conclusions While the rate of thromboembolic events in our series was 19%, the overall morbidity was only 2%. This highlights the fact that even complex MCA aneurysms can safely and effectively be treated by endovascular means with or without the use of balloon or stent assistance, as long as the interventionalist is astutely aware of the possibility of thrombus formation and acts accordingly with thrombolytic therapy when necessary.

Second primary malignancies in retinoblastoma patients treated with intra-arterial chemotherapy: the first 10 years.

BACKGROUND/AIMS: Survivors of retinoblastoma carry a lifetime risk of secondary malignancies. It is well established that external beam radiation increases this risk; however, the risk with ophthalmic artery chemosurgery (OAC) remains unknown. We report on 10 years of experience with OAC and the rate of second primary malignancy (SPM) development. METHODS: This is a single-centre retrospective review approved by the Memorial Sloan Kettering Cancer Center Institutional Review Board of all patients who received OAC over a 10-year period, from May 2006 to November 2016. The second tumour incidence and survival in patients with germline disease (bilateral and unilateral with family history or confirmed germline mutation) was estimated using the Kaplan-Meier method. Patients who received external beam radiotherapy were excluded from analyses. RESULTS: Two hundred and thirty-three patients with heritable retinoblastoma who received OAC were analysed. Nineteen patients were excluded for having received external beam radiation. The Kaplan-Meier estimate of the likelihood for SPM development was 2.7% at 5 years (95% CI 0 to 25). All of the SPMs were pineoblastomas and all patients had bilateral disease in this cohort. CONCLUSIONS: In our 10-year experience, we have found that SPM development in patients with germline retinoblastoma treated with OAC alone is comparable to previously published rates. In the first 10 years, OAC did not increase the known incidence of SPMs. This cohort will continue to be followed to establish the rate of development with extended follow-up.

Topotecan Delivery to the Optic Nerve after Ophthalmic Artery Chemosurgery.

Extraocular retinoblastoma is a major challenge worldwide, especially in developing countries. Current treatment involves the administration of systemic chemotherapy combined with radiation, but there is a clear need for improvement of chemotherapy bioavailability in the optic nerve. Our aim was to study the ophthalmic artery chemosurgery (OAC) local route for drug delivery assessing ocular and optic nerve exposure to chemotherapy and to compare it to exposure after intravenous infusion (IV) of the same dose in an animal model. Topotecan was used as a prototype drug that is active in retinoblastoma and based on the extensive knowledge of its pharmacokinetics in preclinical and clinical settings. Five Landrace pigs received 4mg of topotecan via OAC as performed in retinoblastoma patients. At the end of the infusion, the eyes were enucleated, the optic nerve and retina were dissected, and the vitreous and plasma were separated. After recovery and a wash-out period, the animals received a 30-min IV infusion of topotecan (4 mg). The remaining eye was enucleated and tissues and fluids were separated. All samples were stored until quantitation using HPLC. A significantly higher concentration of topotecan in the optic nerve, vitreous, and retina was obtained in eyes after OAC compared to IV infusion (p<0.05). The median (range) ratio between topotecan concentration attained after OAC to IV infusion in the optic nerve, retina and vitreous was 84(54-668), 143(49-200) and 246(56-687), respectively. However, topotecan systemic exposure after OAC and IV infusion remained comparable (p>0.05). The median optic nerve-to-plasma ratio after OAC and IV was 44 and 0.35, respectively. Topotecan OAC delivery attained an 80-fold higher concentration in the optic nerve compared to the systemic infusion of the same dose with similar plasma concentrations in a swine model. Patients with retinoblastoma extension into the optic nerve may benefit from OAC for tumor burden by increased chemotherapy bioavailability in the optic nerve without increasing systemic exposure or toxicity.

INTRAVITREAL MELPHALAN AS SALVAGE THERAPY FOR REFRACTORY RETINAL AND SUBRETINAL RETINOBLASTOMA.

PURPOSE: This case series highlights the novel use of intravitreal melphalan for nonvitreous retinoblastoma. It assesses the efficacy and toxicity of intravitreal melphalan for nonvitreous retinoblastoma. METHODS: This observational small case series investigates three patients treated with intravitreal melphalan for nonvitreous retinoblastoma that was refractory to multiple-course ophthalmic artery chemosurgery. Patients' demographics, response to treatment, and toxicity of treatment as clinically evaluated are measured by electroretinogram. PATIENTS: Three eyes of three patients received a median of 7 weekly intravitreal melphalan injections (30 µg/0.07 cc) for persistent retinal or subretinal tumors refractory to treatment with multiple-course ophthalmic artery chemosurgery. RESULTS: Eyes remain tumor free at a median of 14-month follow-up. One eye was enucleated because of a vitreous hemorrhage that obscured fundus details. One eye had extinguished electroretinogram recordings before injections and two eyes had a decrease in electroretinogram responses over the intravitreal treatment course. The eye with subretinal seeding demonstrated marked retinopathy by ophthalmoscopy and fluorescein angiography and one eye was enucleated because of the development of a vitreous hemorrhage. CONCLUSION: This small case series highlights that nonvitreous disease that is, refractory or persistent despite previous ophthalmic artery chemosurgery can regress with intravitreal melphalan. However, this treatment may result in retinal toxicity.

Intraarterial chemotherapy for kissing macula tumors in retinoblastoma.

PURPOSE: To describe the management of kissing macula retinoblastoma tumors treated with intraarterial chemotherapy. METHODS: Superselective infusion of chemotherapy (combinations of melphalan, topotecan, and carboplatin) into the ophthalmic artery of children with retinoblastoma who had kissing macula tumors was administered on an outpatient basis. Results were assessed with indirect ophthalmoscopy, RetCam digital photography, B-scan ultrasonography, and electroretinograms. Three children with bilateral retinoblastoma (aged 6.1, 7, and 16 months) and kissing macula tumors in an eye were treated. RESULTS: All children are alive without the need for removal of the eye, systemic chemotherapy, or external beam irradiation. In each case, the kissing tumors retracted, leaving an anatomically normal fovea. Final 30-Hz flicker electroretinograms were 93.9, 65, and 63.9 µV (under anesthesia). There were no significant systemic toxicities. CONCLUSION: Superselective infusion of chemotherapy by means of the ophthalmic artery of young children with kissing macula tumors resulted in prompt shrinkage of tumors away from the fovea. There were no systemic side effects.

Spontaneously Resolving Periocular Erythema and Ciliary Madarosis Following Intra-arterial Chemotherapy for Retinoblastoma.

PURPOSE AND DESIGN: To describe an unusual clinical finding seen in children undergoing intra-arterial chemotherapy for retinoblastoma. MATERIALS AND METHODS: A retrospective review of 69 eyes of 63 patients receiving intra-arterial chemotherapy over a 3-year period. Charts and photographs of 69 consecutive cases were reviewed, and data were collected on patients with clinical evidence of a hyperemic cutaneous periocular abnormality following the procedure. RESULTS: A blanching erythematous and edematous patch was noted in the periocular region in 16% (11 of 69) of the children who received intraarterial chemotherapy. The plaque extended into the region of the supertrochlear and medial marginal artery distribution on the ipsilateral side of the intra-arterial chemotherapy. All patches of erythema spontaneously resolved within 3 months following completion of the intra-arterial chemotherapy. CONCLUSION: Periocular erythema and swelling is a self-limited clinical finding associated with intra-arterial chemotherapy in a small number of patients.

Aneurysms of the posterior circulation: detection and treatment planning using volume-rendered three-dimensional helical computerized tomography angiography.

OBJECT: The aim of this study was to determine whether computerized tomography (CT) angiography could be used to identify and characterize aneurysms of the posterior circulation and guide optimal treatment selection, and how data obtained using this method compared with intraoperative findings. METHODS: Patients suspected of harboring brain aneurysms underwent CT angiography and digital subtraction (DS) angiography; the results were prospectively interpreted by blinded independent evaluators. All patients with posterior circulation aneurysms were consecutively enrolled in the study. After treatment, neurosurgeons and endovascular therapists evaluated the ability of CT and DS angiography to demonstrate features of the lesions important for triage between treatment options (Wilcoxon signed-rank test) and to allow for coil or clip preselection and complete treatment planning (McNemar test of proportions), while using intraoperative findings as the basis of truth. In 242 patients overall, CT angiography detected 38 aneurysms and two aneurysmal blisters in 32 patients. The sensitivity of CT angiography in revealing posterior circulation aneurysms was 100% compared with DS angiography, with no false-positive results. Furthermore, CT angiography was sufficient as the sole study at triage for 65% of the posterior circulation aneurysms (26 of 40 lesions; p < 0.001), including 62% of the complex lesions (p < 0.001), and permitted coil or clip preselection in 74% of treated cases (20 of 27 cases; p < 0.002). Results of CT angiography revealed information about mural calcification and intraluminal thrombus not available on DS angiography, which affected patient care. CONCLUSIONS: In this study population, CT angiography was comparable to DS angiography in the detection and characterization of aneurysms of the posterior circulation. Computerized tomography angiography was used successfully to triage patients between endovascular and neurosurgical treatment options in a significant proportion of cases and permitted treatment planning in more than 70% of treated cases.