Complex intracranial aneurysms: a DELPHI study to define associated characteristics.

PURPOSE: Intracranial aneurysms present significant health risks, as their rupture leads to subarachnoid haemorrhage, which in turn has high morbidity and mortality rates. There are several elements affecting the complexity of an intracranial aneurysm. However, criteria for defining a complex intracranial aneurysm (CIA) in open surgery and endovascular treatment could differ, and actually there is no consensus on the definition of a "complex" aneurysm. This DELPHI study aims to assess consensus on variables defining a CIA. METHODS: An international panel of 50 members, representing various specialties, was recruited to define CIAs through a three-round Delphi process. The panelists participated in surveys with Likert scale responses and open-ended questions. Consensus criteria were established to determine CIA variables, and statistical analysis evaluated consensus and stability. RESULTS: In open surgery, CIAs were defined by fusiform or blister-like shape, dissecting aetiology, giant size (≥ 25 mm), broad neck encasing parent arteries, extensive neck surface, wall calcification, intraluminal thrombus, collateral branch from the sac, location (AICA, SCA, basilar), vasospasm context, and planned bypass (EC-IC or IC-IC). For endovascular treatment, CIAs included giant size, very wide neck (dome/neck ratio ≤ 1:1), and collateral branch from the sac. CONCLUSIONS: The definition of aneurysm complexity varies by treatment modality. Since elements related to complexity differ between open surgery and endovascular treatment, these consensus criteria of CIAs could even guide in selecting the best treatment approach.

Idiopathic intracranial hypertension secondary to Superior Sagittal Sinus Stenosis: a case report.

INTRODUCTION: Idiopathic intracranial hypertension (IIH) is a disease characterized by elevated intracranial pressure (ICP) without established etiology. Venous sinus stenosis contributes to IIH; however, it is still uncertain whether the stenosis is a primary cause of IIH or a secondary result in response to elevated ICP. Transverse sinus stenosis is frequently identified in patients with IIH and it is suggestive of raised ICP. Here, we report a case of IIH caused by intrinsic superior sagittal sinus stenosis (SSS). CASE PRESENTATION: A 43-year-old man suffered from IIH with headache, papilledema, and visual impairment. Angiography demonstrated isolated SSS stenosis with a pressure gradient of 30 mmHg. SSS stenosis was resistant to revascularization by stenting alone and intrastent balloon angioplasty was then performed to overcome such resistance. The rigidity of the vein wall suggests that the vein is not collapsed and the stenosis is intrinsic, secondary to idiopathic anatomical local changes. Post-procedure headache disappeared and visual acuity improved. CONCLUSION: An isolated SSS stenosis could lead to intracranial hypertension and this condition should be taken into account in the diagnostic workup of IIH. By now, SSS stenosis is not mentioned in any current consensus guidelines or paper on the diagnostic workflow of intracranial hypertension.

Understanding the role of randomization in clinical research and practice.

BACKGROUND: The scientific role randomization plays in clinical research is universally recognized, but poorly understood. In stark contrast, the ethical role randomization plays in the proper care of patients in the presence of uncertainty has been almost completely ignored. METHODS: We review the introduction of randomization in the design of experiments, its first use in Britain, and its essential role in analysis of statistical results. We also review Thomas Chalmers' argument from 1975 that showed the ethical role randomization can play in the care of patients. We discuss how Chalmers' vision can be generalized to all contexts of clinical uncertainty. DISCUSSION: Randomization is not only essential to the validity of statistical tests, it is also the best way to learn from experience. Although Chalmers' admonition to 'Randomize the first patient' pertained to the use of innovations, the notion that randomized allocation can be done in the best interest of patients is generalizable to all medical or surgical interventions that have yet to be proven beneficial, opening the perspective that care research can be integrated into practice in the best medical interest of patients. CONCLUSION: Randomized allocation plays crucial scientific and ethical roles both in research and practice. It is the most efficient way to learn from experience. Prior to this gain in knowledge, it is the way to optimize care in the presence of uncertainty.

Watch brain circulation in unexplained progressive myelopathy: a review of Cognard type V arterio-venous fistulas.

BACKGROUND: Intracranial dural arterio-venous fistulas are pathological anastomoses between arteries and veins located within dural sheets and whose clinical manifestations depend on location and hemodynamic features. They can sometimes display perimedullary venous drainage (Cognard type V fistulas-CVFs) and present as a progressive myelopathy. Our review aims at describing CVFs' variety of clinical presentation, investigating a possible association between diagnostic delay and outcome and assessing whether there is a correlation between clinical and/or radiological signs and clinical outcomes. METHODS: We conducted a systematic search on Pubmed, looking for articles describing patients with CVFs complicated with myelopathy. RESULTS: A total of 72 articles for an overall of 100 patients were selected. The mean age was 56.20 ± 14.07, 72% of patients were man, and 58% received an initial misdiagnosis. CVFs showed a progressive onset in 65% of cases, beginning with motor symptoms in 79% of cases. As for the MRI, 81% presented spinal flow voids. The median time from symptoms' onset to diagnosis was 5 months with longer delays for patients experiencing worse outcomes. Finally, 67.1% of patients showed poor outcomes while the remaining 32.9% obtained a partial-to-full recovery. CONCLUSIONS: We confirmed CVFs' broad clinical spectrum of presentation and found that the outcome is not associated with the severity of the clinical picture at onset, but it has a negative correlation with the length of diagnostic delay. We furthermore underlined the importance of cervico-dorsal perimedullary T1/T2 flow voids as a reliable MRI parameter to orient the diagnosis and distinguish CVFs from most of their mimics.

Coating (Coating to Optimize Aneurysm Treatment in the New Flow Diverter Generation) study. The first randomized controlled trial evaluating a coated flow diverter (p64 MW HPC): study design.

BACKGROUND: Due to its high efficacy, flow diversion is increasingly used in the management of unruptured and recanalized aneurysms. Because of the need for perioperative dual antiplatelet treatment (DAPT), flow diversion is not indicated for the treatment of ruptured aneurysms. To overcome this major limitation, surface modification-'coating'-of flow diverters has been developed to reduce platelet aggregation on the implanted device, reduce thromboembolic complications, and facilitate the use of coated flow diverter treatment in patients with single antiplatelet treatment (SAPT). COATING (Coating to Optimize Aneurysm Treatment in the New Flow Diverter Generation) is a prospective, randomized, multicenter trial that aims to determine whether the use of the coated flow diverter p64 MW HPC under SAPT is non-inferior (or even superior) to the use of the bare flow diverter p64 MW under DAPT in relation to thromboembolic and hemorrhagic complications. METHODS: Patients with unruptured or recanalized aneurysms for which endovascular treatment with a flow diverter is indicated will be enrolled and randomly assigned on a 1:1 ratio to one of two treatment groups: p64 MW HPC with SAPT or p64 MW with DAPT. RESULTS: The primary endpoint is the number of diffusion-weighted imaging lesions visualized via MRI assessed within 48 hours (±24 hours) of the index procedure. Secondary primary endpoints are comparing safety and efficacy in both arms. CONCLUSIONS: This randomized controlled trial is the first to directly compare safety and efficacy of coated flow diverters under SAPT with bare flow diverters under DAPT. TRIAL REGISTRATION NUMBER: http://clinicaltrials.gov/ - NCT04870047.

Flow Diverter Devices in the Treatment of Anterior Communicating Artery Region Aneurysms: Would the Regional Anatomy and the Aneurysm Location Affect the Outcomes?

BACKGROUND: In this study, the authors evaluated the efficacy and the safety of flow diverter devices (FDD) in anterior communicating artery (ACoA) region aneurysms, focusing on anatomical factors that could affect the outcome, such as the location of the aneurysm along the ACoA (centered on ACoA or decentered on the A1-A2 junction) and the anatomy of the ACoA region. METHODS: Clinical, procedural and follow-up data were analyzed. Aneurysms were classified according to the location along the ACoA (centered or decentered on the A1-A2 junction) and on the basis of the anatomical configuration of the ACoA region. Safety was assessed by recording intraprocedural, periprocedural and delayed complications to determine the morbidity and mortality rates. The functional outcome was evaluated with the modified Rankin scale (mRS) prior to and after the endovascular procedure. To assess the efficacy, midterm and long-term clinical, angiographic and cross-sectional imaging follow-ups were recorded. Subgroup analysis according to the different ACoA regional anatomical configurations and the ACoA aneurysm locations were performed. RESULTS: 33 patients (17 males; 16 females) with ACoA region aneurysms were treated with FDDs. 27 aneurysms were located at the A1-A2 junction (82%) while the remaining six aneurysms were centered on the ACoA. No mortality was recorded. The overall morbidity rate was 6% (2/33 procedures). Major complications occurred in 33% (2/6) of ACoA aneurysms and in the 0% of A1-A2 junction aneurysms. Mid-term and long-term neuroimaging follow-ups showed the occlusion of the aneurysm in 28/33 cases (85%). Complete occlusion rates were 93% in the A1-A2 junction aneurysms and 50% in ACoA aneurysms. CONCLUSIONS: The FDD is a safe and effective tool that can be used in the treatment of selected cases of ACoA region aneurysms. The location of the aneurysm along the ACoA and the regional anatomy of the ACoA complex could affect the efficacy and safety.

Flow diverter devices in the treatment of complex middle cerebral artery aneurysms when surgical and endovascular treatments are challenging.

OBJECTIVE: In this study, the authors retrospectively evaluated the effectiveness and the safety of non-surgical middle cerebral artery (MCA) aneurysms treated via the implantation of a flow diverter device (FDD). METHODS: Clinical, procedural and follow-up data were analyzed in order to evaluate the safety and effectiveness of the treatment with the FDD in complex MCA aneurysms. Safety was assessed recording (intra-procedural, peri-procedural and delayed) complications in order to determine the morbidity and mortality rates. Functional outcome was evaluated with modified Rankin Scale (mRS) prior and after the endovascular procedure. To assess the efficacy, midterm and long-term clinical, angiographic and cross-sectional imaging follow-ups were recorded. RESULTS: 47 patients (21 males; 26 females) with MCA aneurysms were treated with FDD. 7 were ruptured. 21 aneurysms were saccular, 19 dissecting, 3 fusiform, 2 blood blister-like and 2 were pseudo-aneurysms. 14 aneurysms were small, 23 large and 10 giant, with a mean size of 15.3 mm. 8 aneurysms were recurrent (Raymond-Roy class III): 2 patients had an aneurysmal sac recanalization after being treated with simple coiling and 6 after being treated with microsurgical clipping. In 4 cases (8.5%), more than one FDD was telescopically positioned in order to treat the aneurysm, for a total of 54 FDDs used. The overall mortality rate was 2.1% (1/47) and the overall morbidity rate was 8.6% (4/47). Midterm neuroimaging follow-ups showed the complete occlusion of the aneurysm in 63% cases, which became 91% at the end of the follow-up. CONCLUSIONS: FDD is a safe and effective tool that can be used in the treatment of complex MCA aneurysms, where conventional neurosurgical treatments can be challenging or ineffective.

Neutrophils predominate the immune signature of cerebral thrombi in COVID-19 stroke patients.

Coronavirus disease 2019 (COVID-19) is associated with an increased risk of thrombotic events. Ischemic stroke in COVID-19 patients entails high severity and mortality rates. Here we aimed to analyze cerebral thrombi of COVID-19 patients with large vessel occlusion (LVO) acute ischemic stroke to expose molecular evidence for SARS-CoV-2 in the thrombus and to unravel any peculiar immune-thrombotic features. We conducted a systematic pathological analysis of cerebral thrombi retrieved by endovascular thrombectomy in patients with LVO stroke infected with COVID-19 (n = 7 patients) and non-covid LVO controls (n = 23). In thrombi of COVID-19 patients, the SARS-CoV-2 docking receptor ACE2 was mainly expressed in monocytes/macrophages and showed higher expression levels compared to controls. Using polymerase chain reaction and sequencing, we detected SARS-CoV-2 Clade20A, in the thrombus of one COVID-19 patient. Comparing thrombus composition of COVID-19 and control patients, we noted no overt differences in terms of red blood cells, fibrin, neutrophil extracellular traps (NETs), von Willebrand Factor (vWF), platelets and complement complex C5b-9. However, thrombi of COVID-19 patients showed increased neutrophil density (MPO+ cells) and a three-fold higher Neutrophil-to-Lymphocyte Ratio (tNLR). In the ROC analysis both neutrophils and tNLR had a good discriminative ability to differentiate thrombi of COVID-19 patients from controls. In summary, cerebral thrombi of COVID-19 patients can harbor SARS-CoV2 and are characterized by an increased neutrophil number and tNLR and higher ACE2 expression. These findings suggest neutrophils as the possible culprit in COVID-19-related thrombosis.

Flow Diversion for Acutely Ruptured Intracranial Aneurysms Treatment: A Retrospective Study and Literature Review.

OBJECTIVE: Flow diversion is becoming an increasingly established practice for the treatment of acutely ruptured intracranial aneurysms. In this study the authors present a literature review and meta-analysis, adding a retrospective review of institutional registry on emergency treatment of aRIA with flow diverter stent. MATERIALS AND METHODS: A systematic search of PubMed, SCOPUS, Ovid MEDLINE, and Ovid EMBASE was performed on April 20th, 2021, extrapolating 35 articles. R language 'meta' and 'metafor' packages were used for data pooling. The DerSimonian-Laird model was used to calculate the pooled effect. The I2 value and Q statistic evaluated study heterogeneity. Additionally, the authors retrospectively reviewed their institutional database for the treatment and outcomes of all patients with acutely ruptured intracranial aneurysms treated with flow diverter stent placement from May 2010 to November 2020 was performed. RESULTS: From the systematic literature review and meta-analysis, the pooled proportion of complete aneurysm occlusion was 78%, with a pooled rate of 79%, 71%, 80%, and 50% for dissecting, saccular, fusiform, and mycotic aneurysms, respectively. The pooled proportion of aneurysm rebleeding and intrastent stenosis was 12% and 15% respectively, for a total of 27% rate. The analysis of authors retrospective register showed an overall mortality rate of 16.7% (3/18), with a low but not negligible postprocedural rebleeding and intrastent thrombosis rates (5.6% and 11.1% respectively). CONCLUSION: Although increasingly utilized in the management of selected patients with acutely ruptured intracranial aneurysms, flow diversion for acutely ruptured intracranial aneurysms treatment presents rebleeding and intrastent stenosis rates not negligible.

A minimally invasive approach for giant middle cerebral artery thrombosed aneurysms treatment.

BACKGROUND: Management of complex thrombosed aneurysms of the middle cerebral artery (MCA) is challenging. Lesions not amenable to endovascular techniques or direct clipping might require a bypass procedure with subsequent aneurysm occlusion. Various bypass techniques followed by surgical or endovascular closure of the aneurysm are available, but an unpredictable extension of the thrombus to the parent vessel and/or to perforator vessels can occur. We presented a multidisciplinary technique with the aim to reduce invasiveness and complications. METHODS: We present two patients, harboring a thrombosed giant MCA bifurcation aneurysm, who were treated with a minimally invasive three-steps multimodality procedure. In both cases, through a limited exposure of the sylvian fissure, a side-to-side anastomosis between the two M2 branches was performed, followed in the immediate postop by an endovascular occlusion of the frontal M2 branch, with the aim of transforming a bifurcation aneurysm in a sidewall aneurysm, that was then treated a few days later by flow diverter deployment. RESULTS: Both patients had excellent outcomes and were discharged after 7 days without neurological deficits. CONCLUSIONS: Treatment of complex thrombosed MCA aneurysms is challenging. Side-to-side M2 anastomosis with the aim of transforming a bifurcation aneurysm in a sidewall aneurysm, suitable to be treated few days later by flow diverter deployment, offers a minimally invasive multimodal approach with the possibility of reducing serious complications.

Focal Cerebral Arteriopathy in a Young Adult Following SARS-CoV2 Reinfection.

Ten days after SARS-Cov2 reinfection with mild gastrointestinal symptoms and headache that occurred 2 months after an initial infection, a previously healthy 37-year-old woman developed fluctuating facial and upper limb paresthesia and weakness. Diffusion-weighted magnetic resonance imaging revealed ischemic lesions in the right parietal region of different stages within the same vascular territory. A cerebral angiography demonstrated an isolated focal arteriopathy with no other arterial involvement. Focal cerebral arteriopathy is exceedingly rare among adults and most commonly triggered by varicella-zoster virus reactivation. We present a case of focal cerebral arteriopathy in a patient with a recent reinfection with SARS-CoV-2.

Long-term follow-up of the Derivo® Embolization Device (DED®) for intracranial aneurysms: the Italian Multicentric Registry.

BACKGROUND: The flow-diverter devices (FDDs) safety and effectiveness have been demonstrated by large series and meta-analyses. Due to the high occlusion rates and the acceptable morbidity rates of FDDs, the indications for their use are continuously expanding. We presented our Italian multicentric experience using the second generation of DERIVO® Embolization Device (DED®; Acandis, Pforzheim, Germany) to cure cerebral aneurysms, evaluating both middle and long-term safety and efficacy of this device. METHODS: Between July 2016 and September 2017 we collected 109 consecutive aneurysms in 108 patients treated using DED® during 109 endovascular procedures in 34 Italian centers (100/109 aneurysms were unruptured, 9/109 were ruptured). The collected data included patient demographics, aneurysm location and characteristics, baseline angiography, adverse event and serious adverse event information, morbidity and mortality rates, and pre- and post-treatment modified Rankin Scale scores. Midterm and long-term clinical, angiographic and cross-sectional CT/MR follow-up were recorded and collected until December 2018. RESULTS: In 2/109 cases, DED® placement was classified as technical failures. The overall mortality and morbidity rates were respectively 6.5% and 5.5%. Overall DERIVO® related mortality and morbidity rates were respectively 0% and 4.6% (5 out of 108 patients). Midterm neuroimaging follow-up showed the complete or nearly complete occlusion of the aneurysm in 90% cases, which became 93% at long-term follow-up. Aneurysmal sac shrinking was observed in 65% of assessable aneurysms. CONCLUSIONS: Our multicentric experience using DED® for endovascular treatment of unruptured and ruptured aneurysms showed a high safety and efficacy profile, substantially equivalent or better compared to the other FDDs.

Endovascular Treatment of Symptomatic Intracranial Vertebrobasilar Stenosis: A 10-Year Single Centre Experience Using Balloon-Expandable Coronary Artery Stents.

BACKGROUND: Symptomatic intracranial vertebro-basilar stenoses (SIVBS) are associated with high risk of recurrent ischemic stroke, even in patients receiving the best medical treatment. Although medical treatment is still the standard of care, non-responding patients may require endovascular treatment; balloon-mounted coronary stents (BMCS) could be successfully employed. This study aims to retrospectively analyze our high volume Interventional Neurovascular center ten-year experience in the off-label use of BMCS for the treatment of SIVBS, in order to assess its feasibility and safety. METHODS: We retrospectively analyzed all consecutive patients with SIVBS treated with BMCS in the last ten years in our center. Data collected included patient demographics, stenosis location and characteristics, early (<30 days) and late (>30 days) stroke and death rates, pre-symptomatic and post-treatment modified Rankin Scale (mRS) scores. RESULTS: 42 patients (35 males, average age 65,7 ± 10,7, range 37-85) with SIVBS were treated with BMCS. Thirty-four (80,9%) patients were symptomatic despite ongoing best medical therapy; eight (19,1%) patients were treated in emergency for large vessel occlusion, due to an underlying stenosis. BMCSs were successfully deployed in all cases. The incidence of stroke and death at one month was 7,1% (3/42). The incidence of TIA, stroke and death at long-term follow-up (average time of 3 years) was 14,3% (4,7 per 100 person-years). At long-term follow-up, mRS improved in 82% of patients who underwent elective treatment. CONCLUSIONS: In our experience, the off-label use of BMCS in the endovascular treatment of SIVBS resistant to medical treatment is feasible and safe.

Comaneci-Assisted Coiling Embolization of a Posttraumatic Carotid-Cavernous Fistula.

BACKGROUND: A direct carotid-cavernous fistula (CCF) is a rare complication that typically occurs in closed head injuries. The balloon-assisted occlusion is the most used treatment. However, this technique requires multiple inflation/deflations, which could be problematic in a vessel with acute vessel injury. CASE DESCRIPTION: In this study we reported a case of 72-year-old male patient with posttraumatic CCF, treated endovascularly with a transarterial Comaneci-assisted coiling embolization, highlighting the advantages and pitfalls of this innovative endovascular treatment. CONCLUSIONS: The Comaneci-assisted coiling technique has proven to be advantageous both in the microcatheterization of the CCF and during coiling with remodeling technique. In addition, this device does not interrupt the vascular flow compared to balloon-assisted coiling and does not require long-term antiaggregation therapy with respect to the stent placement.

Comprehensive Aneurysm Management (CAM): An All-Inclusive Care Trial for Unruptured Intracranial Aneurysms.

BACKGROUND: In the absence of randomized evidence, the optimal management of patients with unruptured intracranial aneurysms (UIA) remains uncertain. METHODS: Comprehensive Aneurysm Management (CAM) is an all-inclusive care trial combined with a registry. Any patient with a UIA (no history of intracranial hemorrhage within the previous 30 days) can be recruited, and treatment allocation will follow an algorithm combining clinical judgment and randomization. Patients eligible for at least 2 management options will be randomly allocated 1:1 to conservative or curative treatment. Minimization will be used to balance risk factors, using aneurysm size (≥7 mm), location (anterior or posterior circulation), and age <60 years. RESULTS: The CAM primary outcome is survival without neurologic dependency (modified Rankin Scale [mRS] score <3) at 10 years. Secondary outcome measures include the incidence of subarachnoid hemorrhage during follow-up and related morbidity and mortality; morbidity and mortality related to endovascular treatment or surgical treatment of the UIA at 1 year; overall morbidity and mortality at 1, 5, and 10 years; when relevant, duration of hospitalization; and, when relevant, discharge to a location other than home. The primary hypothesis for patients randomly allocated to at least 2 options, 1 of which is conservative management, is that active UIA treatment will reduce the 10-year combined neurologic morbidity and mortality (mRS score >2) from 24% to 16%. At least 961 patients recruited from at least 20 centers over 4 years will be needed for the randomized portion of the study. CONCLUSIONS: Patients with unruptured intracranial aneurysms can be comprehensively managed within the context of an all-inclusive care trial.