European Reference Network for Rare Vascular Diseases (VASCERN) position statement on cerebral screening in adults and children with hereditary haemorrhagic telangiectasia (HHT).

Hereditary haemorrhagic telangiectasia (HHT) is a multisystemic vascular dysplasia inherited as an autosomal dominant trait. Approximately 10 % of patients have cerebral vascular malformations, a proportion being cerebral arteriovenous malformations (AVMs) and fistulae that may lead to potentially devastating consequences in case of rupture. On the other hand, detection and treatment related-risks are not negligible, and immediate. While successful treatment can be undertaken in individual cases, current data do not support the treatment of unruptured AVMs, which also present a low risk of bleeding in HHT patients. Screening for these AVMs is therefore controversial.Structured discussions, distinctions of different cerebrovascular abnormalities commonly grouped into an "AVM" bracket, and clear guidance by neurosurgical and neurointerventional radiology colleagues enabled the European Reference Network for Rare Vascular Disorders (VASCERN-HHT) to develop the following agreed Position Statement on cerebral screening:1) First, we emphasise that neurological symptoms suggestive of cerebral AVMs in HHT patients should be investigated as in general neurological and emergency care practice. Similarly, if an AVM is found accidentally, management approaches should rely on expert discussions on a case-by-case basis and individual risk-benefit evaluation of all therapeutic possibilities for a specific lesion.2) The current evidence base does not favour the treatment of unruptured cerebral AVMs, and therefore cannot be used to support widespread screening of asymptomatic HHT patients.3) Individual situations encompass a wide range of personal, cultural and clinical states. In order to enable informed patient choice, and avoid conflicting advice, particularly arising from non-neurovascular interpretations of the evidence base, we suggest that all HHT patients should have the opportunity to discuss knowingly brain screening issues with their healthcare provider.4) Any screening discussions in asymptomatic individuals should be preceded by informed pre-test review of the latest evidence regarding preventative and therapeutic efficacies of any interventions. The possibility of harm due to detection of, or intervention on, a vascular malformation that would not have necessarily caused any consequence in later life should be stated explicitly.We consider this nuanced Position Statement provides a helpful, evidence-based framework for informed discussions between healthcare providers and patients in an emotionally charged area.

Giant intracranial aneurysms: natural history and 1-year case fatality after endovascular or surgical treatment.

OBJECTIVE: Clinical evidence on giant intracranial aneurysms (GIAs), intracranial aneurysms with a diameter of at least 25 mm, is limited. The authors aimed to investigate the natural history, case fatality, and treatment outcomes of ruptured and unruptured GIAs. METHODS: In this international observational registry study, patients with a ruptured or unruptured GIA received conservative management (CM), surgical management (SM), or endovascular management (EM). The authors investigated rupture rates and case fatality. RESULTS: The retrospective cohort comprised 219 patients with GIAs (21.9% ruptured GIAs and 78.1% unruptured GIAs) whose index hospitalization occurred between January 2006 and November 2016. The index hospitalization in the prospective cohort (362 patients with GIAs [17.1% ruptured and 82.9% unruptured]) occurred between December 2008 and February 2017. In the retrospective cohort, the risk ratio for death at a mean follow-up of 4.8 years (SD 2.2 years) after CM, compared with EM and SM, was 1.63 (95% CI 1.23-2.16) in ruptured GIAs and 3.96 (95% CI 2.57-6.11) in unruptured GIAs. In the prospective cohort, the 1-year case fatality in ruptured GIAs/unruptured GIAs was 100%/22.0% during CM, 36.0%/3.0% after SM, and 39.0%/12.0% after EM. Corresponding 1-year rupture rates in unruptured GIAs were 25.0% during CM, 1.2% after SM, and 2.5% after EM. In unruptured GIAs, the HR for death within the 1st year in patients with posterior circulation GIAs was 6.7 (95% CI 1.5-30.4, p < 0.01), with patients with a GIA at the supraclinoid internal carotid artery as reference. Different sizes of unruptured GIAs were not associated with 1-year case fatality. CONCLUSIONS: Rupture rates for unruptured GIAs were high, and the natural history and treatment outcomes for ruptured GIAs were poor. Patients undergoing SM or EM showed lower case fatality and rupture rates than those undergoing CM. This difference in outcome may in part be influenced by patients in the CM group having been found poor candidates for SM or EM.Clinical trial registration no.: NCT02066493 (clinicaltrials.gov).

Treatment of intracranial aneurysms using the pipeline flex embolization device with shield technology: angiographic and safety outcomes at 1-year follow-up.

PURPOSE: The Pipeline Embolization Device (PED) is a routine first-line treatment option for intracranial aneurysms (IAs). The Pipeline Flex Embolization Device with Shield Technology (Pipeline Shield) is an updated version of the PED which has been modified to include a surface phosphorylcholine biocompatible polymer. Its early technical success and safety have been reported previously. Here, we assessed the long-term safety and efficacy of the Pipeline Shield for the treatment of IAs. MATERIALS AND METHODS: The Pipeline Flex Embolization Device with Shield Technology (PFLEX) study was a prospective, single-arm, multicenter study for the treatment of unruptured IAs using the Pipeline Shield. The primary endpoint was a major stroke in the territory supplied by the treated artery or neurologic death at 1-year post-procedure. Angiographic outcomes were also assessed by an independent radiology laboratory at 6 months and 1 year. RESULTS: Fifty patients (mean age, 53 years; 82% female) with 50 unruptured IAs were treated. Mean aneurysm diameter was 8.82±6.15 mm. Of the target aneurysms, 38/50 (76%) were small (<10 mm), 11/50 (22%) were large (≥10 and<25 mm), and 1/50 (2%) was giant (≥25 mm). Forty-seven (94%) were located in the internal carotid artery and three (6%) in the vertebral artery. At 1-year post-procedure, no major strokes or neurologic deaths were reported, and complete occlusion was achieved in 27/33 (81.8%). There were no instances of aneurysm recurrence or retreatment. CONCLUSIONS: Our 1-year follow-up concerning angiographic and safety outcomes corroborate previous evidence that the Pipeline Shield is a safe and effective treatment for IAs. TRIAL REGISTRATION NUMBER: NCT02390037.

Torcular Meningioma with Multi-Venous Sinus Invasion: Compensatory Drainage Veins and Surgical Strategy.

BACKGROUND: Torcular meningiomas involving major dural venous sinuses are rare entities and a great challenge for neurosurgeons. The deep knowledge of the patency of occlusion of the sinuses, the extent of the occlusion and potentially new developing of extra and intracranial collateral venous drainage as compensatory venous channels, are at the base of a correct operative strategy. CASE DESCRIPTION: A 45-year-old woman presented with persistent headache. Magnetic resonance imaging of the brain and digital subtraction angiography demonstrated a huge torcular meningioma with complete multi-venous sinus occlusion and a wide venous network for brain and tumor drainage. In these rare cases, we have hypothesized the presence of venous drainage shared by the brain and the tumor, which could generate undesirable venous occlusion during operative resection. This could be a cause of the well-known surgical complications, such as brain swelling and hemorrhagic infarction. CONCLUSIONS: We report our experience with a huge torcular meningioma with multi-venous sinus invasion and a literature review, with a special emphasis on compensatory drainage veins and surgical strategy.

Unruptured Versus Ruptured AVMs: Outcome Analysis from a Multicentric Consecutive Series of 545 Surgically Treated Cases.

BACKGROUND: Recent literature strongly challenged indications to perform preventive surgery in unruptured arteriovenous malformation (AVM) claiming that invasive AVM treatment is associated with a significant risk of complications and thus conservative management may be a preferable alternative in many patients. On the other hand, the recent improvement of surgical instrumentation and treatment strategies (both surgical and interventional) yielded better outcomes than those achieved only a decade ago. Therefore, even among specialists, a wide variety of opinions, concerning the treatment of unruptured AVM, can be found. METHODS: This multicenter retrospective study analyzes a consecutive series of 545 surgically treated AVMs in 10 different hospitals in Italy. RESULTS: Patients with AVMs treated after hemorrhage had an unfavorable (modified Rankin Scale score >1) outcome in more than one third (37.69%) of the cases. Conversely, with proper indications, unruptured AVMs treated preventively have a good outcome in 93.8% of cases, increasing to 95.7%, with no death, if only Spetzler-Martin grades 1-3 are considered (P < 0.05). Outcomes on discharge significantly (P < 0.05) improve at 6 months with the disappearance of many of the initial neurologic deficits that turn out to be transient. CONCLUSIONS: In unruptured low-risk AVMs (Spetzler-Martin grades 1-3), over time, the risk of surgery-associated neurologic deficits becomes lower than that linked to spontaneous hemorrhage, with a crossover point at 6.5 years. Because the average bleeding age is less than 45 years, preventive surgery can be advocated to safeguard the patient and overcome the risks associated with the natural history of AVMs.

Periprocedural outcomes and early safety with the use of the Pipeline Flex Embolization Device with Shield Technology for unruptured intracranial aneurysms: preliminary results from a prospective clinical study.

BACKGROUND AND PURPOSE: The Pipeline Embolization Device (PED) has become a routine first-line option for treatment of intracranial aneurysms (IAs). We assessed the early safety and technical success of a new version of PED, Pipeline Flex Embolization Device with Shield Technology (Pipeline Shield), which has the same design and configuration but has been modified to include a surface synthetic biocompatible polymer. MATERIALS AND METHODS: The Pipeline Flex Embolization Device with Shield Technology (PFLEX) study is a prospective, single-arm, multicenter study for the treatment of unruptured IAs using Pipeline Shield. The primary study endpoints included the occurrence of major stroke in the territory supplied by the treated artery or neurologic death at 1 year post-procedure. Secondary endpoints included the rate of Pipeline Shield-related or procedure-related serious or non-serious adverse events. Analyses were conducted to evaluate early safety findings in the 30-day post-procedure period as well as technical procedural success outcomes. RESULTS: Fifty patients with 50 unruptured target IAs were enrolled. Mean aneurysm diameter was 8.82±6.15 mm. Thirty-eight aneurysms (76%) were small (<10 mm). Device deployment was technically successful with 98% of devices. Complete wall apposition was achieved immediately post-procedure in 48 cases (96%). No major strokes or neurologic deaths were reported in the 30-day post-procedure period. CONCLUSIONS: The results of this first experience with the new Pipeline Flex corroborate the early safety of the device. Mid-term and long-term follow-up examinations will provide data on safety outcomes at the 6-month and 1-year follow-up periods. CLINICAL TRIAL REGISTRATION: NCT02390037.

Bilateral inferior petrosal sinus sampling.

Simultaneous bilateral inferior petrosal sinus sampling (BIPSS) plays a crucial role in the diagnostic work-up of Cushing's syndrome. It is the most accurate procedure in the differential diagnosis of hypercortisolism of pituitary or ectopic origin, as compared with clinical, biochemical and imaging analyses, with a sensitivity and specificity of 88-100% and 67-100%, respectively. In the setting of hypercortisolemia, ACTH levels obtained from venous drainage of the pituitary are expected to be higher than the levels of peripheral blood, thus suggesting pituitary ACTH excess as the cause of hypercortisolism. Direct stimulation of the pituitary corticotroph with corticotrophin-releasing hormone enhances the sensitivity of the procedure. The procedure must be undertaken in the presence of hypercortisolemia, which suppresses both the basal and stimulated secretory activity of normal corticotrophic cells: ACTH measured in the sinus is, therefore, the result of the secretory activity of the tumor tissue. The poor accuracy in lateralization of BIPSS (positive predictive value of 50-70%) makes interpetrosal ACTH gradient alone not sufficient for the localization of the tumor. An accurate exploration of the gland is recommended if a tumor is not found in the predicted area. Despite the fact that BIPSS is an invasive procedure, the occurrence of adverse events is extremely rare, particularly if it is performed by experienced operators in referral centres.

Position statement from the Italian Society of Neurosurgery on the ARUBA Study.

As the conclusions of the ARUBA Study are strongly oriented towards therapeutic abstention, we think it is appropriate to express the concern of the Italian Society of Neurosurgery for the impact that this study might have on the health of patients, if not properly evaluated. The vast majority of patients (76-81%) included in the study was treated with endovascular or radiotherapy treatments, alone or in combination. Only 18 patients (19%) had surgery. It is well known that a partial treatment of arteriovenous malformations (AVMs), as is often the case with endovascular therapy, may increase the risk of bleeding. The primary endpoint (death or symptomatic stroke) in the treated group was reached in 30.7%, i.e. almost one-third of the subjects. This has no comparison in the current surgical literature. Considering permanent and transient neurological deficits along with headaches and seizures all together in the same outcome evaluation parameter may be inappropriate and misleading. The graph with all results from the ARUBA Study, which claims to be the demonstration that natural history is better that treatment, clearly shows that what is assumed to be treated has not actually been treated. If death or stroke occur a few years from treatment, it only means that the disease was not cured and patients received a partial - therefore ineffective, if not dangerous - treatment. An effective treatment, as surgery is, must have a flat follow-up curve. The ARUBA Study shows that incomplete treatment leads to negative outcome, confirming that an integrated multidisciplinary strategy has to be plotted out before starting any treatment and that a complete exclusion of the AVM must be achieved.

Curative Reconstruction of Giant Fusiform Intracranial Aneurysms with Flow-Diverter and Self-expanding Stents.

OBJECTIVE AND IMPORTANCE: To demonstrate the curative reconstruction of two giant fusiform aneurysms using a combination of flow-diverter stents and self-expanding stents for intracranial use. CLINICAL PRESENTATION: Two cases that would have been difficult to manage with standard methods: one patient with deficiencies of cranial nerves VI and VII on the left, acute diplopia, and an aneurysm of the vertebrobasilar bifurcation, the other with diplopia, deficiencies of cranial nerves III and VI, and an aneurysm of the intracavernous internal carotid artery. INTERVENTION OR TECHNIQUE: Complete reconstruction was achieved using a combination of flow-diverter and self-expandable stents. Follow-up investigations at 6 months demonstrated the complete reconstruction of the arteries and angiographically determined disappearance of the aneurysms with resolution of the clinical profile. The patients' outcome was excellent (modified Rankin Scale: 0). CONCLUSION: This technique enables safe and definitive treatment of lesions that would be difficult to manage with other methods. The greater metal surface does not seem to interfere with the perforating arteries originating from the segments involved.

Transvenous approach for the treatment of direct carotid cavernous fistula following Pipeline embolization of cavernous carotid aneurysm: a report of two cases and review of the literature.

Flow diverters are increasingly used for the endovascular treatment of cerebral aneurysms. A rare complication from flow diversion is delayed aneurysm rupture, which can lead to carotid-cavernous fistula (CCF) in the setting of cavernous carotid aneurysms (CCAs). Direct CCFs pose unique management challenges, given the lack of transarterial access to the fistula. We present two cases of direct CCFs following treatment of CCAs with the Pipeline embolization device (PED). Case 1 was a middle-aged patient with a symptomatic 10 mm wide-necked left CCA. Six weeks after PED treatment the patient developed diplopia secondary to direct CCF. Case 2 was a middle-aged patient with a symptomatic 17 mm left CCA treated with PED. One-month follow-up angiography demonstrated a direct CCF. Both patients underwent successful coil embolization of the CCF through a transvenous approach. Direct CCF formation following PED deployment for CCA is a rare complication. Parent vessel sacrifice may be avoided with transvenous occlusion of the fistula.

Onyx embolization of dural arteriovenous fistulas of the cavernous sinus through the superior pharyngeal branch of the ascending pharyngeal artery.

We report three cases of dural arteriovenous fistula (DAVF) of the cavernous sinus treated by Onyx injection through the superior pharyngeal branch of the ascending pharyngeal artery. The treatment of choice of DAVFs of the cavernous sinus is endovascular, and it is preferentially done via transvenous occlusion of the cavernous sinus. The cavernous sinus can be reached through either the inferior petrosal sinus or the superior ophthalmic vein. When these venous routes are occluded, the first attempt is to pass through the occluded inferior petrosal sinus, but sometimes this attempt can fail. In some cases there are small transosseous feeders to the fistula arising from the superior pharyngeal branch of the ascending pharyngeal artery. When all of the more conventional approaches are unattainable, this route can be attempted. In our experience, it allowed safe and rapid occlusion of the fistula.

Transvenous approach for the treatment of direct carotid cavernous fistula following Pipeline embolization of cavernous carotid aneurysm: a report of two cases and review of the literature.

Flow diverters are increasingly used for the endovascular treatment of cerebral aneurysms. A rare complication from flow diversion is delayed aneurysm rupture, which can lead to carotid-cavernous fistula (CCF) in the setting of cavernous carotid aneurysms (CCAs). Direct CCFs pose unique management challenges, given the lack of transarterial access to the fistula. We present two cases of direct CCFs following treatment of CCAs with the Pipeline embolization device (PED). Case 1 was a middle-aged patient with a symptomatic 10 mm wide-necked left CCA. Six weeks after PED treatment the patient developed diplopia secondary to direct CCF. Case 2 was a middle-aged patient with a symptomatic 17 mm left CCA treated with PED. One-month follow-up angiography demonstrated a direct CCF. Both patients underwent successful coil embolization of the CCF through a transvenous approach. Direct CCF formation following PED deployment for CCA is a rare complication. Parent vessel sacrifice may be avoided with transvenous occlusion of the fistula.

Venous flow rearrangement after treatment of cerebral arteriovenous malformations: a novel approach to evaluate the risks of treatment.

OBJECTIVE: This study aims to identify the angiographic parameters that could help predict the risks of hyperemic complications (HCs) in the treatment of cerebral arteriovenous malformations (AVMs). METHODS: The charts and the pre- and post-treatment angiographies of 400 consecutively treated patients with cerebral AVMs were retrospectively reviewed. Several parameters were analyzed: grade, size, drainage depth, number of the "recruited veins" (veins coming from the brain and joining the main AVM drainage), and "venous times" (the times of visualization of the nidus and the main drainage, of the "recruited veins," and finally of the normal cerebral veins). On this basis, two groups were identified: group 1, consisting of 309 patients (77.3%) with normal/subnormal venous times, and group 2, consisting of 91 patients (22.7%) with altered venous times and venous engorgement. Finally, the weight of the various parameters was measured by univariate and multivariate analyses. RESULTS: An overall number of 245 patients (61.2%) achieved favorable outcomes. HCs occurred in a total of 28 patients (7%): No patient belonged to group 1, so that these adverse effects were reported in 30.7% of group 2 patients. The presence of deep drainage and the number of recruited veins resulted in statistically significantly different impacts on the risk of the different grades. CONCLUSIONS: The statistical analysis allowed the identification of three different risk scores, which were named Nig-scores (Niguarda scores). Nig-score 0 means no risk of HCs and concerns patients without altered venous times; Nig-score 1 represents patients with intermediate risk, that is, with moderately altered venous times and few recruited veins; Nig-score 2 indicates high risk of HCs and refers to patients with markedly altered venous times.