BACKGROUND AND PURPOSE: Early brain injury is a major determinant of clinical outcome in poor-grade (World Federation of Neurosurgical Societies [WFNS] IV?V) aneurysmal SAH and is radiologically defined by global cerebral edema. Little is known, though, about the effect of global intracranial hemorrhage volume on early brain injury development and clinical outcome. MATERIALS AND METHODS: Data from the multicentric prospective Poor-Grade Aneurysmal Subarachnoid Hemorrhage (POGASH) Registry of consecutive patients with poor-grade aneurysmal SAH admitted from January 1, 2015, to August 31, 2022, was retrospectively evaluated. Poor grade was defined according to the worst-pretreatment WFNS grade. Global intracranial hemorrhage volume as well as the volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH were calculated by means of analytic software in a semiautomated setting. Outcomes included severe global cerebral edema (defined by Subarachnoid Hemorrhage Early Brain Edema Score grades 3?4), in-hospital mortality (mRS 6), and functional independence (mRS 0?2) at follow-up. RESULTS: Among 400 patients (median global intracranial hemorrhage volume of 91?mL; interquartile range, 59?128), severe global cerebral edema was detected in 218/400 (54.5%) patients. One hundred twenty-three (30.8%) patients died during the acute phase of hospitalization. One hundred fifty-five (38.8%) patients achieved mRS 0?2 at a median of 13 (interquartile range, 3?26) months of follow-up. Multivariable analyses showed global intracranial hemorrhage volume as independently associated with severe global cerebral edema (adjusted OR, 1.009; 95% CI, 1.004?1.014; P < .001), mortality (adjusted OR, 1.006; 95% CI, 1.001?1.01; P = .018) and worse clinical outcome (adjusted OR, 0.992; 95% CI, 0.98?0.996; P < .010). The effect of global intracranial hemorrhage volume on clinical-radiologic outcomes changed significantly according to different age groups (younger than 50, 50?70, older than 70?year of age). Volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH affected the 3 predefined outcomes differently. Intracerebral hemorrhage volume independently predicted global cerebral edema and long-term outcome, intraventricular hemorrhage volume predicted mortality and long-term outcome, and SAH volume predicted long-term clinical outcome. CONCLUSIONS: Global intracranial hemorrhage volume plays a pivotal role in global cerebral edema development and emerged as an independent predictor of both mortality and long-term clinical outcome. Aging emerged as a reducing predictor in the relationship between global intracranial hemorrhage volume and global cerebral edema.

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.

BACKGROUND:Inflammation is emerging as an essential trigger for thrombosis. In the interplay between innate immunity and coagulation cascade, neutrophils and neutrophil extracellular traps (NETs) can promote thrombus formation and stabilization. In ischemic stroke, it is uncertain whether the involvement of the inflammatory component may differ in thrombi of diverse etiology. We here aimed to evaluate the presence of neutrophils and NETs in cerebral thrombi of diverse etiology retrieved by endovascular thrombectomy (EVT).METHODS:We performed a systematic histological analysis on 80 human cerebral thrombi retrieved through EVT in acute ischemic stroke patients. Thrombus composition was investigated in terms of neutrophils (MPO+ cells) and NET content (citH3+ area), employing specific immunostainings. NET plasma content was determined and compared to NET density in the thrombus.RESULTS:Neutrophils and NETs were heterogeneously represented within all cerebral thrombi. Thrombi of diverse etiology did not display a statistically significant difference in the number of neutrophils (p = 0.51). However, NET content was significantly increased in cardioembolic compared to large artery atherosclerosis thrombi (p = 0.04), and the association between NET content and stroke etiology remained significant after adjusted analysis (beta coefficient = -6.19, 95%CI = -11.69 to -1.34, p = 0.01). Moreover, NET content in the thrombus was found to correlate with NET content in the plasma (p ≤ 0.001, r = 0.62).CONCLUSION:Our study highlights how the analysis of the immune component within the cerebral thrombus, and specifically the NET burden, might provide additional insight for differentiating stroke from diverse etiologies.

Few studies have evaluated the relationship between brain arteriovenous malformations (bAVMs) angioarchitecture and the response to Gamma Knife Stereotactic Radiosurgery (GKSR). A prospectively enrolled single-center cohort of patients with bAVMs treated by GKSR has been studied to define independent predictors of obliteration with particular attention to angioarchitectural variables. Only patients older than 18 years old (y.o.), who underwent baseline digital subtraction angiography (DSA) and clinico-radiological follow-up of at least 36 months, were included in the study. Data of 191 patients were evaluated. After a mean follow-up of 80 months (range 37–173), total obliteration rate after first GKSR treatment was 66%. Mean dose higher than 22 Gy (P = .019, OR = 2.39, 95% CI 1.15–4.97) and flow rate dichotomized into high vs non-high (P < .001, OR = 0.23, 95% CI 0.11–0.51) resulted to be independent predictors of obliteration. Flow-surrogate angioarchitectural features did not emerge as independent outcome predictors. Flow rate seems to be associated in predicting outcome after GKSR conferring high-flow AVM a lower occlusion rate. Its role should be considered when planning radiosurgical treatment of bAVM, and it could be added to other parameters used in GKRS outcome predicting scales.

The search for aetiology in ischemic stroke represents one of the most challenging, costly and critical issues to set up adequate secondary prevention strategies. However, despite extensive clinical examinations, up to one-third of ischemic strokes have no established cause (cryptogenic stroke) [ [1] Hart R.G. Catanese L. Perera K.S. Ntaios G. Connolly S.J. Embolic stroke of undetermined source: a systematic review and clinical update. Stroke. 2017; 48: 867-872https://doi.org/10.1161/STROKEAHA.116.016414 Crossref PubMed Scopus (305) Google Scholar ]. In patients with two or more potential risk factors for stroke, final aetiology often cannot be properly defined. Moreover, even when a major risk factor is present, e.g., atrial fibrillation or atherosclerotic vessel stenosis, stroke aetiology often remains presumptive. Up to day most aetiologic stroke diagnoses are not supported by histopathological analysis. With recent advances in mechanical thrombectomy, the analysis of retrieved cerebral thrombi is emerging as an additional tool to support aetiologic diagnosis [ [2] Bacigaluppi M. Semerano A. Gullotta G.S. Strambo D. Insights from thrombi retrieved in stroke due to large vessel occlusion. J. Cereb. Blood Flow Metab. 2019; 39: 1433-1451https://doi.org/10.1177/0271678X19856131 Crossref PubMed Scopus (38) Google Scholar ], and, in selected cases, it can already clarify the stroke cause [ [3] Semerano A. Genchi A. Callea M. Sanvito F. Simionato F. Panni P. Scomazzoni F. Doglioni C. Comi G. Falini A. Filippi M. Roveri L. Bacigaluppi M. Thrombus hallmarks reveal atherothrombotic stroke aetiology. J. Neurol. 2019; 266: 1533-1535https://doi.org/10.1007/s00415-019-09279-z Crossref PubMed Scopus (3) Google Scholar , [4] Wollenweber F.A. Remi J. Bauer A. Theiss H. Massberg S. Patzig M. Faber C. Dieterich M. Janssen H. Thrombectomy recovers an aortic wall fragment from middle cerebral artery immediately after TAVI. Neurology. 2016; 86: 2111-2112https://doi.org/10.1212/WNL.0000000000002722 Crossref PubMed Scopus (6) Google Scholar ] with potential therapeutic relevance. We here report a case of large vessel stroke with middle cerebral artery (MCA) occlusion with peculiar neuroradiological and histopathological features that aided in clarifying the aetiology of stroke.

The use of lumbar drain (LD) in the aneurysmal subarachnoid hemorrhage (aSAH) has been described to reduce cerebral vasospasm and delayed cerebral ischemia (DCI), with a lack of studies referring to high grade population. The purpose of our study is to assess safety and feasibility of LD in the poor grade aSAH population subjected to endovascular aneurysm occlusion. Twenty-four consecutive poor grade aSAH patients, defined as grade IV and V according to World Federation of Neurological Surgeons (WFNS) classification, subjected to endovascular aneurysm occlusion, were retrospectively reviewed. Details of CSF drainage via LD and related complications were analyzed. Ventriculo-lumbar pressure gradient (VLPG) lower than 6 mmHg was considered in order to start LD use. Good outcome was defined as modified Rankin Scale (mRS) 0-2. LD was started within 72 h since aSAH in 17 cases (70.8%), and in 7 cases (29.2%) it was delayed due to contraindications. The mean LD length was of 13.8 days. The median VLPG during drainage was 2 mmHg (IQR: 0-4). No cases of brain or spinal hemorrhage, permanent neurological worsening due to brain herniation were noted. Three cases (12.5%) of CSF infection and a related death (4.2%) were reported. The use of LD, in association with external ventricular drain (EVD), seems to be safe and feasible in the poor grade aSAH population. VLPG monitoring seems to play a key role in avoiding potentially severe complications.

Volumetric assessment of aneurysmal bleeding has been evaluated in few studies and emerged as a promising outcome predictor. There is a lack of studies evaluating its impact in the poor-grade population. Retrospective review of 63 consecutive poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients, defined as grade IV and V according to the World Federation of Neurological Surgeons (WFNS) classifications. Global intracranial bleeding volume was calculated with its subarachnoid, intracerebral (ICH), and intraventricular (IVH) portions by means of analytical software. Univariate and multivariate analyses were performed in order to identify independent predictors of outcome. Good outcome was defined as modified Rankin Scale (mRS) 0–2 and mortality as mRS 6. The cutoff values of bleeding volumes were derived by receiver operating curve (ROC) analysis. Mean follow-up was of 12.5 (± 1.5) months. Thirty (47.7%) patients achieved good outcome, whereas 19 (30.2) patients out of 63 died. Global intracranial bleeding resulted as an independent predictor of good outcome (cutoff 24 mL). Furthermore, ICH relative percentage of global volume (10% of total) and pure SAH (64% of total) emerged respectively as independent predictors of worsened and improved outcome. Global bleeding volume (cutoff 51 mL) along with global cerebral edema showed to independently predict mortality in the examined poor-grade aSAH population. Volumetric assessment of aneurysmal bleeding has the potential for identifying cutoff values that independently predict outcome. Further insights into the relative importance of different bleeding volumes may be implicated in better tailoring the management of this dismal aSAH population.

Background. Extracranial vertebral artery aneurysms are a rare cause of embolic stroke; surgical and endovascular therapy options are debated and long-term complication may occur. Case Report. A 53-year-old man affected by neurofibromatosis type 1 (NF1) came to our attention for recurrent vertebrobasilar embolic strokes, caused by a primary giant, partially thrombosed, fusiform aneurysm of the left extracranial vertebral artery. The aneurysm was treated by endovascular approach through deposition of Guglielmi Detachable Coils in the proximal segment of the left vertebral artery. Six years later the patient presented stroke recurrence. Cerebral angiography and Color Doppler Ultrasound well characterized the unique hemodynamic condition developed over the years responsible for the new embolic event: the aneurysm had been revascularized from its distal portion by reverse blood flow coming from the patent vertebrobasilar axis. A biphasic Doppler signal in the left vertebral artery revealed a peculiar behavior of the blood flow, alternately directed to the aneurysm and backwards to the basilar artery. Surgical ligation of the distal left vertebral artery and excision of the aneurysm were thus performed. Conclusion. This is the first described case of NF1-associated extracranial vertebral artery aneurysm presenting with recurrent embolic stroke. Complete exclusion of the aneurysm from the blood circulation is advisable to achieve full resolution of the embolic source.

To investigate the role of orbital color Doppler ultrasound (OCDUS) in the diagnosis of carotid-cavernous fistula (CCF) with anterior drainage and particularly whether a negative OCDUS could avoid an invasive diagnostic cerebral angiography (DSA).

We first report the case of a 14-year-old boy, previously treated with a modified Fontan operation at the age of 2, who underwent an intra-arterial thrombolysis for an ischemic stroke with a favorable outcome. No controlled randomized trials on thrombolysis among childhood stroke have been conducted yet. This and other similar cases suggest that thrombolysis may also be safe and beneficial in pediatric patients and those cases may benefit from a prompt access to specialized stroke centers.

The role of 3DTOF MRA in the follow up (FU) of coiled cerebral aneurysms is well established. Though CEMRA (Contrast Enhanced Magnetic Resonance Angiography) has demonstrated to be superior to 3DTOF MRA in showing aneurysms residual patency, its role is still debated. The aim of this study was to verify if there is an added value of CEMRA in the long term follow up of coiled treated aneurysms.