Endovascular reconstruction of unruptured intradural vertebral artery dissecting aneurysms with the Pipeline embolization device.

BACKGROUND: Dissecting aneurysms of the vertebral artery (VA) are difficult to treat using current surgical and endovascular techniques. OBJECTIVE: To analyze retrospectively the efficacy and safety of flow diverters in the treatment of dissecting aneurysms of the vertebral artery. METHODS: We identified six patients with six unruptured VA dissecting aneurysms either arising from the V4 or V3-V4 junction that were treated with the Pipeline embolization device (PED) at our institution between July 2012 and February 2015. Among other parameters, technical feasibility of the procedure, procedure-related complications, angiographic results, and clinical outcome were evaluated. RESULTS: PED placement was achieved in all cases and immediate angiography follow-up demonstrated intra-aneurysmal contrast stasis with parent artery preservation. A temporary episode of dysarthria was noted in one patient. Major procedure-related complications were not observed. The 6-month follow-up (n=6) demonstrated complete/near-complete aneurysm obliteration in five patients and partial obliteration in one. At the 1-year follow-up (n=5) stable complete aneurysm occlusion was seen in two patients. Two cases showed progression from near complete occlusion and partial occlusion at 6 months to complete occlusion and near complete occlusion. One cases showed unchanged near complete occlusion. No aneurysmal bleeding, in-stent stenosis or thromboembolic complication was seen. National Institutes of Health Stroke Scale and modified Rankin scale scores remained unchanged from admission to discharge. CONCLUSIONS: Our preliminary experience with the use of PED for the treatment of intradural VA dissecting aneurysms shows promising short-term results, making this technique a feasible and safe treatment option in patients suitable for this approach. However, long-term and larger cohort studies are needed to validate these results.

Stent-assisted coil embolization of aneurysms with small parent vessels: safety and efficacy analysis.

BACKGROUND: Stent-assisted coil embolization (SACE) is a viable therapeutic approach for wide-neck intracranial aneurysms. However, it can be technically challenging in small cerebral vessels (≤2 mm). OBJECTIVE: To present our experience with stents approved for SACE in aneurysms with small parent arteries. METHODS: All patients who underwent stent-assisted aneurysm treatment with either a Neuroform or an Enterprise stent device at our institution between June 2006 and October 2012 were identified. Additionally, we evaluated each patient's vascular risk factors, aneurysm characteristics (ruptured vs non-ruptured, incidental finding, recanalized) and follow-up angiography data. RESULTS: A total of 41 patients with 44 aneurysms met our criteria, including 31 women and 10 men. Most of the aneurysms were located in the anterior circulation (75%). Stent placement in vessels 1.2-2 mm in diameter was successful in 93.2%. Thromboembolic complications occurred in 6 cases and vessel straightening was seen in 1 case only. Initial nearly complete to complete aneurysm obliteration was achieved in 88.6%. Six-month follow-up angiography showed coil compaction in three cases, one asymptomatic in-stent stenosis and stent occlusion. Twelve to 20-months' follow-up showed stable coil compaction in two patients compared with previous follow-up, and aneurysm recanalization in two patients. Twenty-four to 36-months' follow-up showed further coil compaction in one of these patients and aneurysm recanalization in a previous case of stable coil compaction on mid-term follow-up. CONCLUSIONS: Our results suggest that SACE of aneurysms with small parent vessels is feasible in selected cases and shows good long-term patency rates of parent arteries.

Onyx embolization in distal dissecting posterior inferior cerebellar artery aneurysms.

BACKGROUND: Dissecting aneurysms located along the distal segments of the posterior inferior cerebellar artery (PICA) are extremely rare, accounting for only 0.5-0.7% of all intracranial aneurysms. Treatment of these aneurysms is challenging, both surgically and endovascularly. We present our preliminary experience and clinical data utilizing Onyx as an embolization agent in the treatment of these lesions with proximal parent artery preservation. METHODS: 7 consecutive ruptured peripheral PICA aneurysms, in 7 patients, were treated with superselective Onyx embolization at our institutions. According to the anatomical classification of Lister et al, these aneurysms were located in the lateral medullary segment (n=1), tonsillomedullary segment (n=1), and the telovelotonsillary segment (n=5) of the PICA. Technical feasibility, procedure related complications, angiographic results, follow-up diagnostic imaging, and clinical outcome were evaluated. RESULTS: In all cases, endovascular treatment was successful, with complete occlusion of the aneurysm with proximal parent artery preservation at the final postprocedural angiogram. Procedure related complications were not observed. One patient with a poor clinical condition at admission died during the initial hospital stay due to extensive subarachnoid and intraventricular hemorrhage. No rebleeding or recanalization was noted during follow-up. Two patients had a residual moderate to severe disability at follow-up. Favorable outcomes, with no or mild disability, were observed in four of the surviving patients. CONCLUSIONS: Angiographic, diagnostic imaging, and clinical results of our small series indicate that Onyx embolization of dissecting distal PICA aneurysms with parent artery preservation is an effective option with acceptable morbidity and mortality rate, in those cases in which surgical clipping or endovascular coiling of the aneurysmal sac is not suitable.

Flow diverter stents for unruptured saccular anterior circulation perforating artery aneurysms: safety, efficacy, and short-term follow-up.

BACKGROUND: Anterior circulation perforating artery aneurysms including anterior choroidal artery and lenticulostriate artery aneurysms are rare. Injury to these vessels can lead to severe debilitating symptoms. OBJECTIVE: To present a new approach to treatment using flow diversion technology. METHODS: Patients treated with a Pipeline embolization device (PED) for perforator artery aneurysms at our institution between June 2012 and May 2013 were identified and included in our retrospective analysis. We evaluated patient vascular risk factors; family history of aneurysms; aneurysm characteristics; National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) on admission; and angiography follow-up and patient clinical outcome at discharge, 6 months, and 1 year. RESULTS: We included four patients with a mean age of 59.8 years. Two patients had a positive family history of aneurysms. Patient vascular risk factors included smoking, dyslipidemia, and hypertension. All patients presented with a NIHSS and mRS of 0 on admission. Aneurysms were located at the anterior choroidal (n=2) or lenticulostriate artery (n=2) and were treated with a single PED. No periprocedural or postprocedural complications occurred. The patients were discharged with no change in NHISS or mRS score. Six-month and 1-year follow-up angiography showed complete aneurysm occlusion. Mild intimal hyperplasia was seen in 2 cases at 6 months, but was resolved at the 1-year follow-up. No re-treatment was necessary. NIHSS and mRS remained 0 at follow-up time points. CONCLUSIONS: Our preliminary results show that flow diversion technology is an effective and safe therapy for complex, hard-to-treat aneurysms in perforating arteries. Larger studies with long-term follow-up are needed to validate our promising results.

Endovascular treatment of tandem vascular occlusions in acute ischemic stroke.

BACKGROUND AND PURPOSE: Tandem vascular occlusions are an important cause of acute ischemic stroke (AIS) and present unique treatment challenges. We report our experience of managing a subset of AIS patients with extracranial vascular stenting/angioplasty and intracranial revascularization. METHODS: Consecutive patients who presented at three centers with AIS from tandem vascular occlusions confirmed by brain and neck CT imaging were included in the study. We retrospectively analyzed the patient demographics, National Institute of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) score at the time of admission, treatment strategy, angiographic results using the Thrombolysis In Cerebral Infarction (TICI) score, and clinical and imaging follow-up. RESULTS: Twenty-eight patients were included. The mean NIHSS score at admission was 18. Extracranial carotid occlusions with a concomitant middle cerebral artery occlusion were seen in 89.3% of patients (n=25) and vertebral artery combined with basilar artery lesions in 10.7% (n=3). An antegrade approach (ie, treatment of the extracranial lesion first) was used in 24 patients (85.7%). Proximal occlusion recanalization was achieved usually with a stent (n=27; 96.4%). Pursuant to intracranial revascularization techniques, ≥ TICI 2A recanalization was seen in 96.4% of patients. An mRS score of ≤ 2 at 90 days was achieved in 56.5% of patients. CONCLUSIONS: Our study shows preliminary data from three centers on recanalization of tandem occlusions in patients presenting with AIS. There was a preference to revascularize the proximal occlusion using a stent followed by distal recanalization with mechanical thrombectomy, intra-arterial thrombolysis or a combination of these. This approach has low periprocedural complications and can achieve an excellent angiographic and clinical outcome.

Double embolic protection during carotid artery stenting with persistent hypoglossal artery.

A woman presented with 75% stenosis of the right internal carotid artery (ICA) with extension to the origin of a persistent hypoglossal artery (PHA). The PHA is a rare fetal variant of carotid-basilar anastomosis that elevates the risk of ischemia and embolic infarction within the posterior cerebral circulation in patients with carotid disease proximal to the anastomosis. Our case is highly unique because of the extremely rare nature of the PHA with associated ICA stenosis that extended to the PHA. Additionally, a novel treatment approach was employed by stenting and angioplasty while protecting both the anterior and posterior cerebral circulations.

Brd4 links chromatin targeting to HPV transcriptional silencing.

The E2 protein encoded by human papillomaviruses (HPVs) inhibits expression of the viral E6 oncoprotein, which, in turn, regulates p53 target gene transcription. To identify cellular proteins involved in E2-mediated transcriptional repression, we isolated an E2 complex from human cells conditionally expressing HPV-11 E2. Surprisingly, the double bromodomain-containing protein Brd4, which is implicated in cell cycle control and viral genome segregation, was found associated with E2 and conferred on E2 the ability to inhibit AP-1-dependent HPV chromatin transcription in an E2-binding site-specific manner as illustrated by in vitro reconstituted chromatin transcription experiments. Knockdown of Brd4 in human cells alleviates E2-mediated repression of HPV transcription. The E2-interacting domain at the extreme C terminus and the chromatin targeting activity of a bromodomain-containing region are both essential for the corepressor activity of Brd4. Interestingly, E2-Brd4 blocks the recruitment of TFIID and RNA polymerase II to the HPV E6 promoter region without inhibiting acetylation of nucleosomal histones H3 and H4, indicating an acetylation-dependent role of Brd4 in the recruitment of E2 for transcriptional silencing of HPV gene activity. Our finding that Brd4 is a component of the virus-assembled transcriptional silencing complex uncovers a novel function of Brd4 as a cellular cofactor modulating viral gene expression.

Transcriptional activity among high and low risk human papillomavirus E2 proteins correlates with E2 DNA binding.

The full-length E2 protein, encoded by human papillomaviruses (HPVs), is a sequence-specific transcription factor found in all HPVs, including cancer-causing high risk HPV types 16 and 18 and wart-inducing low risk HPV types 6 and 11. To investigate whether E2 proteins encoded by high risk HPVs may function differentially from E2 proteins encoded by low risk HPVs and animal papillomaviruses, we conducted comparative DNA-binding and transcription studies using electrophoretic mobility shift assays and cell-free transcription systems reconstituted with purified general transcription factors, cofactor, RNA polymerase II, and with E2 proteins encoded by HPV-16, HPV-18, HPV-11, and bovine papillomavirus type 1 (BPV-1). We found that although different types of E2 proteins all exhibited transactivation and repression activities, depending on the sequence context of the E2-binding sites, HPV-16 E2 shows stronger transcription activity and greater DNA-binding affinity than those displayed by the other E2 proteins. Surprisingly, HPV-18 E2 behaves more similarly to BPV-1 E2 than HPV-16 E2 in its functional properties. Our studies thus categorize HPV-18 E2 and BPV-1 E2 in the same protein family, a finding consistent with the available E2 structural data that separate the closely related HPV-16 and HPV-18 E2 proteins but classify together the more divergent BPV-1 and HPV-18 E2 proteins.