To investigate predictors and clinical impact of delayed cerebral infarction (CI) in a national multicentric poor grade aneurysmal subarachnoid hemorrhage (aSAH) population. Retrospective analysis of prospectively collected data from the multi-centric POGASH (Poor Grade aSAH) registry of consecutive patients treated from January 1st, 2015, to June 30th, 2023. Poor grade was defined according to the worst-pretreatment WFNS scale. CI was defined as a new ischemic lesion/s within 6 weeks of aSAH onset, not present on CT acquired within 48hrs and not related to treatment or hematoma. Clinical outcome was assessed by the modified Rankin Scale. Among 532 consecutive WFNS grades IV-V aSAH patients, CI occurred in 106 (19.9

The incidence of vertebral osteomyelitis is increasing with heterogeneity in clinical presentation and outcome. Lack of pathogen identification could complicate clinical management. This study aimed to compare the clinical characteristics, management and outcome of patients with vertebral osteomyelitis (VOs) with known aetiology (KAe) and unknown aetiology (UAe). A total of 92 patients with VOs were included, 57 (62%) with KAe and 35 (38%) with UAe. In our cohort, VO with known etiology was more commonly related to a worse clinical presentation, more frequent hospitalization, required more therapeutic lines, and experienced delays in switching to oral therapy.

OBJECTIVE:Intracranial dissecting aneurysms (DAs) are rare and challenging lesions, often associated with high rates of rebleeding and poor clinical outcomes. There is limited evidence regarding optimal treatment strategies, timing, and outcomes, especially in the context of poor-grade subarachnoid hemorrhage (pSAH). The authors aimed to describe the clinical features and treatment outcomes of patients with DAs included in a national multicentric registry of pSAH and to identify independent outcome predictors within this subpopulation. METHODS:The authors conducted a retrospective analysis of prospectively collected data from the multicenter Poor-Grade Aneurysmal Subarachnoid Hemorrhage (POGASH) registry, including consecutive patients admitted between January 1, 2015, and June 30, 2024. Poor grade was defined as a pretreatment World Federation of Neurosurgical Societies grade IV-V. Outcomes were assessed using the modified Rankin Scale. DAs were classified according to the Mizutani classification. RESULTS:Of the 693 consecutive pSAH patients included in the registry, data from 60 patients with DA were analyzed. Among the 54 treated patients, 88.9% underwent endovascular treatment (vessel occlusion [48%], flow diversion [26%], and coiling [26%]), while 11.1% were treated surgically. The median (IQR) time to treatment was 6 (4-9) hours from symptom onset. Rebleeding occurred in 23.3% of patients, significantly more frequently than in the overall cohort (p < 0.048). Rebleeding independently predicted in-hospital mortality (adjusted OR 7.4; 95% CI 1.5-35.1; p = 0.011) and long-term disability (adjusted OR 0.08; 95% CI 0.007-0.98; p = 0.04). Internal carotid artery blister aneurysms were independently associated with rebleeding (adjusted OR 8; 95% CI 1.2-50; p = 0.027). CONCLUSIONS:In the context of pSAH, DAs are characterized by distinct clinicoradiological features and carry a significant risk of ultra-early rebleeding, which strongly influences clinical outcome. These findings suggest a potential benefit of ultra-early or immediate treatment in this patient population, pending further validation.

Disseminated non-tuberculous mycobacteria (dNTM) infections are mostly reported among individuals with an underlying congenital or acquired immunodeficiency or receiving immunosuppressive treatment, but are rarely documented in otherwise healthy subjects. We describe a case of recurrent disseminated mycobacterial infection in an apparently immunocompetent Chinese woman. Mycobacterium szulgai and Mycobacterium avium-complex were identified in distinct episodes. Long-term antimycobacterial therapy was administered given the occurrence of recurrent events when off-treatment. Successful management over more than 10 years and immunologic data are reported. This case-report highlights that dNTM should be suspected also among apparently immunocompetent hosts and that thorough assessment of underling immune-impairments is helpful to define patients’ management. Long-term antimycobacterial therapy and close monitoring is required to grant successful outcomes in case of recurrent dNTM infections.

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.

Arteriovenous malformations’ (AVMs) obliteration depends on several factors; among the many factors that must be considered to obtain a high rate of obliteration and a low rate of complications, Flickinger-Pollock Score (FPS) seems to have an important role but still have to be validated in the pediatric population while Paddick-Conformity Index (PCI) still has no demonstration of its utility on the outcome and is considered only as a treatment quality marker.