The influence of epigenetic biological age on key complications and outcomes in aneurysmal subarachnoid haemorrhage.

BACKGROUND: We aimed to investigate the association between DNA-methylation biological age (B-age) calculated as age acceleration (ageAcc) and key aneurysmal subarachnoid haemorrhage (aSAH) complications such as vasospasm, delayed cerebral ischaemia (DCI), poor outcome, and mortality. METHODS: We conducted a prospective study involving 277 patients with aSAH. B-age was determined in whole blood samples using five epigenetic clocks: Hannum's, Horvath's, Levine's and both versions of Zhang's clocks. Age acceleration was calculated as the residual obtained from regressing out the effect of C-age on the mismatch between C-age and B-age. We then tested the association between ageAcc and vasospasm, DCI and 12-month poor outcome (mRS 3-5) and mortality using linear regression models adjusted for confounders. RESULTS: Average C-age was 55.0 years, with 66.8% being female. Vasospasm occurred in 143 cases (51.6%), DCI in 70 (25.3%) and poor outcomes in 99 (35.7%), with a mortality rate of 20.6%. Lower ageAcc was linked to vasospasm in Horvath's and Levine's clocks, whereas increased ageAcc was associated with 12-month mortality in Hannum's clock. No significant differences in ageAcc were found for DCI or poor outcome at 12 months with other clocks. CONCLUSIONS: Our study indicates that B-age is independently associated with vasospasm and 12-month mortality in patients with aSAH. These findings underscore the potential role of epigenetics in understanding the pathophysiology of aSAH-related complications and outcomes.

Flow diverter stents for endovascular treatment of aneurysms: a comparative study of efficacy and safety between FREDX and FRED.

BACKGROUND: The FRED X flow diverter (FREDX), as the second generation in the FRED series, aims to improve the treatment of cerebral aneurysms. This study compares the efficacy and safety of FREDX with its predecessor, FRED. METHODS: This prospective registry included patients treated with FRED and FREDX devices. Efficacy was assessed using digital subtraction angiography with 3D volumetric reconstruction at immediate and 1 year follow-ups. Safety was evaluated by recording complications, analyzed through univariate contrasts, generalized mixed models, and Bayesian network analyses. RESULTS: We treated 287 patients with 385 aneurysms, with 77.9% receiving FRED and 22.1% FREDX. The median age was 55 years (IQR 47-65) and 78.4% were women. The FREDX group showed a higher prevalence of saccular-like aneurysms (70.6% vs 52.7%, P=0.012) and a higher rate of complete occlusion compared with FRED interventions (79.4% vs 59.3%, P=0.022). After adjusting for confounders, these differences represented a 3.04-fold increased likelihood (95% CI 1.44 to 6.41, P=0.003) of achieving complete occlusion at 1 year with FREDX interventions. Regarding safety, two (3.5%) complications (both non-symptomatic) were observed in the FREDX group and 23 (10.4%) in the FRED group (P=0.166). Bayesian network analysis suggested a trend towards fewer complications for FREDX, with a median reduction of 5.5% in the posterior distribution of the prevalence of complications compared with FRED interventions. CONCLUSIONS: The FREDX device shows improved complete occlusion rates at 1 year compared with the FRED device while maintaining a favourable safety profile, indicating its potential advantage in the treatment of cerebral aneurysms.

Long-term vascular events after subarachnoid hemorrhage.

BACKGROUND: Spontaneous subarachnoid hemorrhage (SAH) long-term risk is not well known. Our aims are: describing long-term vascular event (VE) incidence rates in SAH survivors; describing VE: ischemic and/or hemorrhagic; identifying independent association of factors related to VE; and analyzing the usefulness of factors to increase predictive ability. METHODS: A prospective cohort study of consecutive patients admitted to Hospital del Mar with a diagnosis of SAH (n = 566) between January 2007 and January 2020 was carried out. They were followed up until January 2021. The study endpoint was a new VE in the follow-up. We calculated both incidence rates and cumulative rates at 5 years. Cox regression survival models including vascular risk factors with and without specific data of SAH disease were developed. We analyzed ROC curves of all multivariate models. RESULTS: The analyzed cohort included 423 non-fatal SAH cases. Total patient-years were 2468.16 years. The average follow-up was 70.03 ± 43.14; range: 1-180 months. There were 49 VE detected in 47 patients, as 2 of them had more than 1 VE. Incidence rate was 0.020 events_per_patient/year, cumulative incidence at 5 years was 11.11%. The more frequent VE that we found were cerebrovascular (28/49), mainly ischemic (21/28). Disability after SAH and the presence of multiple aneurysms were independently associated with a VE risk and improved the predictive capacity of multivariate models (AUC 0.679 vs 0.764; p = 0.0062). CONCLUSIONS: We reported a low vascular risk after SAH. We have shown the usefulness of SAH factors to identify patients with a higher risk of VE.

Effect of Intra-arterial Alteplase vs Placebo Following Successful Thrombectomy on Functional Outcomes in Patients With Large Vessel Occlusion Acute Ischemic Stroke: The CHOICE Randomized Clinical Trial.

Importance: It is estimated that only 27% of patients with acute ischemic stroke and large vessel occlusion who undergo successful reperfusion after mechanical thrombectomy are disability free at 90 days. An incomplete microcirculatory reperfusion might contribute to these suboptimal clinical benefits. Objective: To investigate whether treatment with adjunct intra-arterial alteplase after thrombectomy improves outcomes following reperfusion. Design, Setting, and Participants: Phase 2b randomized, double-blind, placebo-controlled trial performed from December 2018 through May 2021 in 7 stroke centers in Catalonia, Spain. The study included 121 patients with large vessel occlusion acute ischemic stroke treated with thrombectomy within 24 hours after stroke onset and with an expanded Treatment in Cerebral Ischemia angiographic score of 2b50 to 3. Interventions: Participants were randomized to receive intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) infused over 15 to 30 minutes (n = 61) or placebo (n = 52). Main Outcomes and Measures: The primary outcome was the difference in proportion of patients achieving a score of 0 or 1 on the 90-day modified Rankin Scale (range, 0 [no symptoms] to 6 [death]) in all patients treated as randomized. Safety outcomes included rate of symptomatic intracranial hemorrhage and death. Results: The study was terminated early for inability to maintain placebo availability and enrollment rate because of the COVID-19 pandemic. Of 1825 patients with acute ischemic stroke treated with thrombectomy at the 7 study sites, 748 (41%) patients fulfilled the angiographic criteria, 121 (7%) patients were randomized (mean age, 70.6 [SD, 13.7] years; 57 women [47%]), and 113 (6%) were treated as randomized. The proportion of participants with a modified Rankin Scale score of 0 or 1 at 90 days was 59.0% (36/61) with alteplase and 40.4% (21/52) with placebo (adjusted risk difference, 18.4%; 95% CI, 0.3%-36.4%; P = .047). The proportion of patients with symptomatic intracranial hemorrhage within 24 hours was 0% with alteplase and 3.8% with placebo (risk difference, -3.8%; 95% CI, -13.2% to 2.5%). Ninety-day mortality was 8% with alteplase and 15% with placebo (risk difference, -7.2%; 95% CI, -19.2% to 4.8%). Conclusions and Relevance: Among patients with large vessel occlusion acute ischemic stroke and successful reperfusion following thrombectomy, the use of adjunct intra-arterial alteplase compared with placebo resulted in a greater likelihood of excellent neurological outcome at 90 days. However, because of study limitations, these findings should be interpreted as preliminary and require replication. Trial Registration: ClinicalTrials.gov Identifier: NCT03876119; EudraCT Number: 2018-002195-40.

The Chemical Optimization of Cerebral Embolectomy trial: Study protocol.

RATIONALE: The potential value of rescue intraarterial thrombolysis in patients with large vessel occlusion stroke treated with mechanical thrombectomy has not been assessed in randomized trials. AIM: The CHemical OptImization of Cerebral Embolectomy trial aims to establish whether rescue intraarterial thrombolysis is more effective than placebo in improving suboptimal reperfusion scores in patients with large vessel occlusion stroke treated with mechanical thrombectomy. SAMPLE SIZE ESTIMATES: A sample size of 200 patients allocated 1:1 to intraarterial thrombolysis or intraarterial placebo will have >95% statistical power for achieving the primary outcome (5% in the control versus 60% in the treatment group) for a two-sided (5% alpha, and 5% lost to follow-up). METHODS AND DESIGN: We conducted a multicenter, randomized, placebo-controlled, double blind, phase 2b trial. Eligible patients are 18 or older with symptomatic large vessel occlusion treated with mechanical thrombectomy resulting in a modified treatment in cerebral ischemia score 2b at end of the procedure. Patients will receive 20-30 min intraarterial infusion of recombinant tissue plasminogen activator or placebo (0.5 mg/ml, maximum dose limit 22.5 mg). STUDY OUTCOME(S): The primary outcome is the proportion of patients with an improved modified treatment in cerebral ischemia score 10 min after the end of the study treatment. Secondary outcomes include the shift analysis of the modified Rankin Scale, the infarct expansion ratio, the proportion of excellent outcome (modified Rankin Scale 0-1), the proportion of infarct expansion, and the infarction volume. Mortality and symptomatic intracerebral bleeding will be assessed. DISCUSSION: The study will provide evidence whether rescue intraarterial thrombolysis improves brain reperfusion in patients with large vessel occlusion stroke and incomplete reperfusion (modified treatment in cerebral ischemia 2b) at the end of mechanical thrombectomy.

A new subtype of intracranial dural AVF according to the patterns of venous drainage.

BACKGROUND AND PURPOSE: A well-known classification of dural arteriovenous fistulas (DAVFs) according to the patterns of venous drainage was described in 1977 by Djindjian, Merland et al. and later revised by Cognard, Merland et al. in 1995. They described 5 types of DAVFs assuming that the type of venous drainage is directly correlated with neurologic symptoms and in particular with hemorrhagic risk. We present a series of cases that combines type IV (DAVF with cortical venous drainage associated with venous ectasia) and type V (DAVF with spinal venous drainage), which we named type IV + V. MATERIALS AND METHODS: A retrospective study between 2012 and 2020 in 2 Hospitals was performed on patients that met inclusion criteria for a diagnosis of this type of DAVF. Demographics, location, clinical presentation and outcomes of endovascular embolization were studied. RESULTS: Five (2,3%) patients out of 220 had a type IV + V DAVF. All cases had an aggressive presentation, either subarachnoid hemorrhage, myelopathy or both. All patients were treated with endovascular transarterial embolization achieving complete angiographic occlusion in one session and total remission of symptoms at 3 months. CONCLUSIONS: This rare type of DAVF, combines two aggressive venous drainage patterns. For that reason, patients with type IV+V DAVF probably have a more aggressive natural history and worst outcome due to risk of intracranial and/or spinal hemorrhage and myelopathy, thus requiring urgent diagnostic and treatment. Larger studies are needed to better understand this type of DAVF.

Short- and long-term outcome of patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVE: To describe short-term and 5-year rates of mortality and poor outcome in patients with spontaneous aneurysmal subarachnoid hemorrhage (aSAH) who received repair treatment. METHODS: In this prospective observational study, mortality and poor outcome (modified Rankin Scale score 3-6) were analyzed in 311 patients with aSAH at 3 months, 1 year, and 5 years follow-up. Sensitivity analysis was performed according to treatment modality. In-hospital and 5-year complications were analyzed. RESULTS: Of 476 consecutive patients with spontaneous subarachnoid hemorrhage, 347 patients (72.9%) had aSAH. Of these, 311 (89.6%) were treated (242 endovascular, 69 neurosurgical), with a mean follow-up of 43.4 months (range, 1 to 145). Three-month, 1-year, and 5-year mortality was 18.4%, 22.9%, and 29.0%, and poor outcome was observed in 42.3%, 36.0%, and 36.0%, respectively. Adjusted poor outcome was lower in endovascular than in neurosurgical treatment at 3 months (odds ratio [OR] 0.36 [95% confidence interval [CI] 0.18-0.74]), with an absolute difference of 15.8% (number needed to treat = 6.3), and at 1 year (OR = 0.40 [95% CI 0.20-0.81]), with an absolute difference of 15.9% (number needed to treat = 6.3). Complications did not differ between the 2 procedures. However, mechanical ventilation was less frequent with the endovascular technique (OR 0.67 [95% CI 0.54-0.84]). CONCLUSIONS: Patients with aSAH treated according to current guidelines had a short-term mortality of 18.4% and 5-year mortality of 29%. The majority (64.0%) of patients remained alive without disabilities at 5-year follow-up. Patients prioritized to endovascular treatment had better outcomes than those referred to neurosurgery because endovascular coiling was not feasible.

Arteriovenous fistulas of the Vein of Galen region in adults: Endovascular treatment.

PURPOSE: Arteriovenous fistulas of the Vein of Galen region in adults (Ad-VGAVF) are an uncommon entity with specific anatomic features. The aim of this article is to present our experience in the endovascular treatment of this pathology and to propose a therapeutic strategy based precisely on the angioarchitecture of these lesions. MATERIALS AND METHODS: During a 20-year period, 10 patients underwent endovascular treatment of Ad-VGAVF. They were nine men and one woman with a mean age of 50 years (23-66 years) treated with the same embolization strategy. Clinical presentation, angiographic characteristics, therapeutic strategy, and clinical outcomes were recorded. RESULTS: All patients were treated exclusively by endovascular approach. Transarterial access was performed in eight patients and combined transvenous and transarterial access in two. Complete obliteration of the fistula was obtained in all patients. There were no intraprocedural complications. Post-embolization neurological symptoms occurred in 5 of 10 with complete resolution at six months in all of them. CONCLUSION: Arteriovenous fistulas of the Vein of Galen region in adults present uniform angioarchitecture despite their low prevalence. Based on this constant angioarchitecture and especially on the features of its venous drainage, judicious embolization strategy is feasible and effective. Ten cases treated entirely by endovascular approach with excellent clinical and angiographic outcomes show this treatment like a curative alternative for this entity of deep topography and severe prognosis.

Efficacy and safety of the dual-layer flow-diverting stent (FRED) for the treatment of intracranial aneurysms.

PURPOSE: To describe the efficacy and complications of treating cerebral aneurysms with the Flow Re-direction Endoluminal Device (FRED) and to identify predictors for aneurysm occlusion. METHODS: A prospective observational registry including all consecutive aneurysms treated with FRED between December 2015 and July 2018 was designed in one therapeutic neuroangiography department. The primary endpoint for treatment efficacy was complete or near-complete occlusion (O'Kelly-Marotta (OKM) C-D), assessed by three-dimensional digital subtraction angiography. Major (all symptomatics) and minor complications were described and those with modified Rankin Scale scores 3-6 were considered clinically relevant. Univariate and multivariate analyses were performed to identify predictors of efficacy. RESULTS: A total of 185 aneurysms were analyzed in 150 patients (mean age 54.3±11.5 years). Mean follow-up was 18.99±11.32 months (range 0-43). Efficacy was evaluated in 156 (84.32%) cases: 132 (84.6%) had OKM C-D occlusion, 31/47 (66%) within the first year and 101/109 (92.7%) later on. Major complications were observed in 12 (6.5%) cases: three strokes (one transient ischemic accident, two minor strokes), six intra-stent thrombosis, and three with bleeding, but only one (0.5%) was clinically relevant. Minor complications (all asymptomatic) were observed in 10 (5.4%) cases: three shortening/repositioning of stent; two arterial dissection, two arterial occlusion, and three intra-stent stenosis. Independent predictors of occlusion were immediate OKM grade B-C-D (OR 4.01, 95% CI 1.51 to 10.62), single aneurysm (OR 3.29, 95% CI 1.05 to 10.32), and small size aneurysm (OR 4.74, 95% CI 1.57 to 14.30). CONCLUSION: The FRED stent fully complied with efficacy and safety requirements for treatment of intracranial aneurysms. Three predictors of aneurysm occlusion were identified.

Misdiagnosis Worsens Prognosis in Subarachnoid Hemorrhage With Good Hunt and Hess Score.

Background and Purpose- Our aim was to describe variables associated with initial misdiagnosis of subarachnoid hemorrhage (SAH). We also analyzed the relationship of misdiagnosis with poor outcome and complications in good Hunt and Hess (HH) cases. Methods- In a prospective cohort of 401 patients with SAH, misdiagnosis was defined as failure to correctly identify, at first physician contact, a subsequently documented SAH; this meant no urgent radiological study and lumbar puncture was performed. Poor outcome was defined as modified Rankin Scale score 3 to 6 at 3-month follow-up. We recorded age, sex, hypertension, diabetes mellitus, current smoking, previous antithrombotic treatment, initial HH and radiological severity, presence of aneurysm, first therapeutic procedure, hydrocephalus, delayed cerebral ischemia (DCI), rebleeding, and procedure-related complications. Results- Misdiagnosis was confirmed in 104/401 (25.9%) patients, who also had a longer time-to-admission to hospital. Misdiagnosis was associated with less clinical and radiological severity, compared with a correct diagnosis; the 2 groups did not differ in age or cardiovascular risk factor profile. Poor outcome was registered in 167/401 patients (41.6%). Age, misdiagnosis, and greater clinical and radiological initial severity were independent predictors of poor outcome. In the 236 patients (58.8% of cohort) with HH 1-2, misdiagnosis was associated with poor outcome in univariate and multivariate analysis, respectively (odds ratio=3.89; 95% CI, 1.89-8.01). Delayed cerebral ischemia (odds ratio=2.47; 95% CI, 1.2-5.09) and procedure-related complications (odds ratio=2.27; 95% CI, 1.07-4.82) were independently associated with misdiagnosis. Conclusions- Misdiagnosis is an unresolved problem in SAH, and it is a missed opportunity for good outcome in patients with HH 1-2. The poor outcome is partially explained by a higher risk of delayed cerebral ischemia and procedure-related complications in misdiagnosed patients. There is a need to improve the diagnostic strategy in patients reporting only a headache (HH 1-2) after SAH.

Castleman's disease as an unusual cause for dysphagia and dyspnea in a pediatric patient.

Castleman's disease is a very rare entity in pediatric population and its presentation in the neck is scarcely described in the literature. We present the case of a 10-year-old-girl with an expanding neck mass over several months causing dysphagia and dyspnea. Surgical excision of the mass was performed and the analysis revealed unicentric Castleman's Disease. This is the second largest reported case of neck pediatric CD in the literature, and it presented with a symptomatology that differs from the other cases described. This fact highlights the need to include CD in the differential diagnosis of pediatric neck masses.

Treatment of Intracranial Aneurysms With the SILK Embolization Device in a Multicenter Study. A Retrospective Data Analysis.

BACKGROUND: Flow-diverter technology has become an important stent-based embolization tool in the treatment of complex cerebrovascular pathology. We report here the experience of 4 Spanish centers with using the SILK flow-diverter (SFD) device. OBJECTIVE: To evaluate the safety and efficacy of using the SFD in the endovascular treatment of intracranial aneurysms with complex morphology. METHODS: We retrospectively examined a prospectively maintained database of patients treated with SFD devices between July 2008 and December 2013 at 1 of 4 institutions in Spain. Data regarding patient demographics, aneurysm characteristics, and technical procedure were analyzed. Angiographic and clinical findings were recorded during the procedure and at 12 months postoperatively. RESULTS: A total of 175 SFD devices were implanted in 157 patients (women/men: 119/38; mean, median, and range of age: 56.2, 56.7, and 19-80 years, respectively), who were treated in a delayed manner (3-6 months from the event) for 180 aneurysms (165 unruptured and 15 ruptured). Adverse events (acute and delayed) were observed in 28.7% of cases (45/157), and most were resolved (19.1%; 30/157). Six months after the procedure, total morbidity and mortality were 9.6% (15/157) and 3.2% (5/157), respectively. Long-term imaging follow-up showed complete occlusion, neck remnants, and residual aneurysm in 78.1% (100/128), 14.0% (18/128), and 7.8% (10/128) of cases, respectively. CONCLUSIONS: The SFD device is an effective tool for the treatment of challenging aneurysms, and allows complete occlusion within a year of the procedure in most patients, with morbidity and mortality comparable to those previously reported for similar devices.

Angioseal™ as a hemostatic device for direct carotid puncture during endovascular procedures.

INTRODUCTION: Direct carotid artery puncture (DCP) is employed in patients with tortuous anatomy and peripheral vascular disease when the peripheral arteries are not available for vascular access. Manual compression is the only method of achieving hemostasis following DCP and, till date, the use of a closure device for DCP has been reported in only one patient. In this study we sought to analyze our experience with the use of closure device for DCP. METHODS: This is a retrospective study of patients in whom Angioseal™ was used following DCP for neuroendovascular procedures. Medical charts and imaging of these patients was reviewed for any abnormalities pertaining to the use of the closure device. RESULTS: A total of eight patients were included in the study. Angioseal™ was used in all the patients. There were no complications related to the use of the closure device in any of the eight patients. Immediate post-procedure angiography done in one patient did not show any structural or hemodynamic abnormalities within the carotid artery lumen. At 6 months follow-up imaging, there was no evidence stenosis or vascular wall abnormality in any of the patients. There were no adverse clinical reactions related to the use of closure device. CONCLUSION: In our experience, Angioseal™ may be a safe and off-label effective closure device for patients undergoing DCP for neuroendovascular procedures. It obviates the need for manual compression without causing any structural or hemodynamic changes within the carotid artery. Larger studies with longer follow-up are required to establish its safety in patients undergoing DCP.

Functional outcome after primary endovascular therapy or IV thrombolysis alone for stroke. An observational, comparative effectiveness study.

BACKGROUND: Among the acute ischemic stroke patients with large vessel occlusions and contraindications for the use of IV thrombolysis, mainly on oral anticoagulation or presenting too late, primary endovascular therapy is often performed as an alternative to the standard therapy even though evidence supporting the use of endovascular reperfusion therapies is not yet established. Using different statistical approaches, we compared the functional independence rates at 3 months among patients undergoing primary endovascular therapy and patients treated only with IV thrombolysis. METHODS: We used data from a prospective, government-mandated and externally audited registry of reperfusion therapies for ischemic stroke (January 2011 to November 2012). Patients were selected if treated with either IV thrombolysis alone (n = 1,582) or primary endovascular thrombectomy (n = 250). A series of exclusions were made to homogenize the clinical characteristics among the two groups. We then carried out multivariate logistic regression and propensity score matching analyses on the final study sample (n = 1,179) to compare functional independence at 3 months, as measured by the modified Rankin scale scores 0-2, between the two groups. RESULTS: The unadjusted likelihood of good outcome was poorer among the endovascular group (OR: 0.69; 95% CI: 0.47-1.0). After adjustment, no differences by treatment modality were seen (OR: 1.51; 95% CI: 0.93-2.43 for primary endovascular therapy). Patients undergoing endovascular thrombectomy within 180-270 min (OR: 2.89; 95% CI: 1.17-7.15) and patients with severe strokes (OR: 1.84; 95% CI: 1.02-3.35) did better than their intravenous thrombolysis counterparts. The propensity score-matched analyses with and without adjustment by additional covariates showed that endovascular thrombectomy was as effective as intravenous thrombolysis alone in achieving functional independence (OR for unadjusted propensity score matched: 1.35; 95% CI: 0.9-2.02, OR for adjusted propensity score matched: 1.45; 95% CI: 0.91-2.32). CONCLUSION: This comparative effectiveness study shows that in ischemic stroke patients with contraindications for IV thrombolysis, primary endovascular treatment might be an alternative therapy at least as effective as IV thrombolysis alone. Randomized controlled trials are urgently needed.

Intra-arterial chemotherapy for retinoblastoma. Challenges of a prospective study.

PURPOSE: To report the efficacy and complications of intra-ophthalmic artery melphalan (IAM) for treatment of patients with advanced intra-ocular retinoblastoma. METHODS: Patients with newly diagnosed, unilateral, group D retinoblastoma were included in a phase II protocol. Children with relapsed-refractory disease after systemic chemoreduction were later treated under the same guidelines.Melphalan (3­5 mg/procedure) was injected through a 1.2 F microcatheter placed into the ophthalmic artery every 21 days. RESULTS: Eleven patients (12 eyes, eight as primary treatment) received 33 IAM procedures. The phase II protocol closed prematurely because of low accrual. The IAM technique was overall safe and could be performed successfully in 31 of 33(94%) attempts. After the second administration of IAM, very good partial response was achieved in all treated eyes. With a median follow-up time of 29.5 months (range 6­57), ocular salvage was achieved in 7 of 12 (58%) eyes. No systemic adverse events were observed. Two patients developed diffuse arteriolar sclerosis, hyperpigmentation of the retinal pigment epithelium and partial retinal atrophy after the second IAM. Both eyes were preserved with no tumour activity, good motility and perception of light, 56 and 30 months after the last IAM treatment. Multinucleated macrophages with intracytoplasmic foreign material were found in the choroid and the retina in 2 of 5 enucleated eyes. CONCLUSION: Our study reports the activity and reproducibility of IAM in advanced retinoblastoma but also underlines the challenges of performing prospective studies on this treatment modality. Toxicity was limited to only ocular vascular events.

Superselective intracerebral catheterization for administration of oncolytic virotherapy in a case of diffuse intrinsic pontine glioma.

New therapies are needed to improve current results in diffuse intrinsic pontine glioma. We present here the initial experience of administering Celyvir, autologous mesenchymal stem cells infected with ICOVIR-5, an oncolytic adenovirus that selectively replicates in cancer cells, by means of superselective intra-arterial delivery, in a patient diagnosed of diffuse intrinsic pontine glioma. Feasibility, safety, and morbidity rates of the superselective catheterization technique are comparable with those of diagnostic angiography. The intra-arterial approach warrants a greater contact of the mesenchymal stem cells with the tumor mass, and minimizes hemorrhages or vascular disruption. The tolerance to the 2 administrations was excellent, with no acute or delayed adverse effect, underscoring the feasibility of this technique for the delivery of virotherapies and/or cellular therapies in this location.

Endovascular treatment of cervical giant perimedullary arteriovenous fistulas.

BACKGROUND: Giant perimedullary arteriovenous fistulas (GPMAVFs) located in the cervical region are a rare pathology with distinctive characteristics. OBJECTIVE: To evaluate clinical presentation and different endovascular treatment options of cervical GPMAVFs and review previously published data in the literature regarding cervical GPMAVFs. METHODS: Six patients with cervical GPMAVFs were found in the spinal vascular malformations database of our group collected between 1990 and 2009. Endovascular techniques and treatment outcomes were evaluated and compared with other published series. RESULTS: Clinical presentations were progressive motor deficit (5 patients), hematomyelia (1 patient), meningeal syndrome (1 patient), and respiratory arrest and gait apraxia (1 patient). Three patients were treated by the transarterial approach. One patient was treated by the transvenous approach due to previous embolizations resulting in a proximal occlusion and preventing a safe transarterial approach. A transvenous approach was used in another patient due to complex arterial anatomy. In 1 patient, direct percutaneous puncture of the venous pouch was necessary because of previous proximal occlusion of the arteries. All embolizations resulted in complete occlusions with clinical improvement, and there was no recanalization during a mean follow-up of 21 months. CONCLUSION: Transarterial embolization of cervical GPMAVFs is safe and effective when it is done in highly experienced centers. Cervical GPMAVFs that cannot be accessed by the transarterial technique due to their complex angioarchitecture can be treated by transvenous embolization or direct puncture of the venous pouch.

Endovascular treatment of a pial arteriovenous fistula of a posteroinferior cerebellar artery with a double origin.

Pial arteriovenous fistulas (pAVF) of the posterior fossa are rare and may present with symptoms secondary to mass effect, venous hypertension or hemorrhage, among others. A case is presented of a previously healthy 2-year-old boy with neurological deficit arising from pAVF of the posteroinferior cerebellar artery. The pAVF was successfully treated with endovascular occlusion.

Carotid artery stenting by direct percutaneous puncture.

Carotid artery stenting is usually performed by a femoral approach. When the patient's anatomy forbids this or other distal access to the carotids, a direct access by percutaneous puncture may be used. We present two cases in which a successful stenting of the carotids with the use of a cerebral protection device was performed.