T1 relaxation: Chemo-physical fundamentals of magnetic resonance imaging and clinical applications.

A knowledge of the complex phenomena that regulate T1 signal on Magnetic Resonance Imaging is essential in clinical practice for a more effective characterization of pathological processes. The authors review the physical basis of T1 Relaxation Time and the fundamental aspects of physics and chemistry that can influence this parameter. The main substances (water, fat, macromolecules, methemoglobin, melanin, Gadolinium, calcium) that influence T1 and the different MRI acquisition techniques that can be applied to enhance their presence in diagnostic images are then evaluated. An extensive case illustration of the different phenomena and techniques in the areas of CNS, abdomino-pelvic, and osteoarticular pathology is also proposed. CRITICAL RELEVANCE STATEMENT: T1 relaxation time is strongly influenced by numerous factors related to tissue characteristics and the presence in the context of the lesions of some specific substances. An examination of these phenomena with extensive MRI exemplification is reported. KEY POINTS: The purpose of the paper is to illustrate the chemical-physical basis of T1 Relaxation Time. MRI methods in accordance with the various clinical indications are listed. Several examples of clinical application in abdominopelvic and CNS pathology are reported.

Methylome analysis of endothelial cells suggests new insights on sporadic brain arteriovenous malformation.

Arteriovenous malformation of the brain (bAVM) is a vascular phenotype related to brain defective angiogenesis. Involved vessels show impaired expression of vascular differentiation markers resulting in the arteriolar to venule direct shunt. In order to clarify aberrant gene expression occurring in bAVM, here we describe results obtained by methylome analysis performed on endothelial cells (ECs) isolated from bAVM specimens, compared to human cerebral microvascular ECs. Results were validated by quantitative methylation-specific PCR and quantitative realtime-PCR. Differential methylation events occur in genes already linked to bAVM onset, as RBPJ and KRAS. However, among differentially methylated genes, we identified EPHB1 and several other loci involved in EC adhesion as well as in EC/vascular smooth muscle cell (VSMC) crosstalk, suggesting that only endothelial dysfunction might not be sufficient to trigger the bAVM phenotype. Moreover, aberrant methylation pattern was reported for many lncRNA genes targeting transcription factors expressed during neurovascular development. Among these, the YBX1 that was recently shown to target the arteridin coding gene. Finally, in addition to the conventional CpG methylation, we further considered the role of impaired CHG methylation, mainly occurring in brain at embryo stage. We showed as differentially CHG methylated genes are clustered in pathways related to EC homeostasis, as well as to VSMC-EC crosstalk, suggesting as impairment of this interaction plays a prominent role in loss of vascular differentiation, in bAVM phenotype.

Predictors of Good Functional Outcome in Patients with Tandem Occlusion After Revascularization Treatment: Single-Center Experience with 12-Month Follow-Up.

OBJECTIVE: The optimal management and procedural strategy for tandem occlusion (TO) in acute ischemic stroke are still unclear, as is the long-term outcome of these patients. The aim of this study was to evaluate predictors of good functional outcome in patients with TO through the analysis of demographics, clinical, and radiological data with a 1-year follow-up. METHODS: We collected data on 100 patients with TO who underwent revascularization treatments in our comprehensive stroke center. We divided patients into 2 groups: those with good functional outcome, defined as a modified Rankin Scale 0-2, and those with poor functional outcome, defined as a modified Rankin Scale 3-6 at 3, 6, and 12-month follow-up. Moreover, we investigated which variables were able to influence mortality. RESULTS: At multivariate analysis, endovascular treatment with mechanical thrombectomy combined with emergent cervical carotid artery stenting was an independent predictor of good functional outcome at 6 and 12 months (adjusted odds ratio [aOR] 4.3, confidence interval [CI] 1.49-12.31, P = 0.007) (aOR 3.5, CI 1.25-9.61, P = 0.017) and was associated with a lower rate of mortality at 3 and 6 months follow-up (aOR 0.14, CI 0.04-0.57, P = 0.006 and aOR 0.296, CI 0.97-0.902, P = 0.032, respectively). Furthermore, smoking habit was associated with a better outcome at 3-month follow-up (aOR 10.7, CI 2.2-51.6, P = 0.003) but not at 6- and 12-month. CONCLUSIONS: Our research, conducted in a small sample size of patients with acute ischemic stroke due to TO of anterior circulation, found that acute stent placement seems to be safe, improving clinical outcome, and it is associated with low rate of mortality at long-term follow-up.

Baseline clinical and neuroradiological predictors of outcome in patients with large ischemic core undergoing mechanical thrombectomy: A retrospective multicenter study.

BACKGROUND: Recent randomized trials have shown the benefit of mechanical thrombectomy (MT) also in patients with an established large ischemic core. AIMS: The purpose of this study was to define baseline predictors of clinical outcome in patients with large vessel occlusion (LVO) in the anterior circulation and an Alberta Stroke Program Early CT score (ASPECTS) ⩽ 5, undergoing MT. MATERIAL AND METHODS: The databases of 16 comprehensive stroke centers were retrospectively screened for patients with LVO and ASPECTS ⩽5 that received MT. Baseline clinical and neuroradiological features, including the differential contribution of all ASPECTS regions to the composite score, were collected. Primary clinical outcome measure was a 90-day modified Rankin Scale (mRS) score of 0-2. Statistical analysis used a logistic regression model and random forest algorithm. RESULTS: A total of 408 patients were available for analysis. In multivariate model, among baseline features, lower age (odd ratio (OR) = 0.962, 95% confidence interval (CI) = 0.943-0.982) and lower National Institute of Health Stroke Scale (NIHSS) score (OR = 0.911, 95% CI = 0.862-0.963) were associated with the mRS score 0-2. Involvement of the M2 (OR = 0.398, 95% CI = 0.206-0.770) or M4 (OR = 0.496, 95% CI = 0.260-0.945) ASPECTS regions was associated with an unfavorable outcome. Random forest analysis confirmed that age and baseline NIHSS score are the most important variables influencing clinical outcome, whereas involvement of cortical regions M5, M4, M2, and M1 can have a negative impact. CONCLUSION: Our retrospective analysis shows that, along with age and baseline clinical impairment, presence of early ischemic changes involving cortical areas has a role in clinical outcome in patients with large ischemic core undergoing MT. DATA ACCESS STATEMENT: The data that support the findings of this study are available upon reasonable request.

Point-Of-Care low-field MRI in acute Stroke (POCS): protocol for a multicentric prospective open-label study evaluating diagnostic accuracy.

INTRODUCTION: Fast and accurate diagnosis of acute stroke is crucial to timely initiate reperfusion therapies. Conventional high-field (HF) MRI yields the highest accuracy in discriminating early ischaemia from haemorrhages and mimics. Rapid access to HF-MRI is often limited by contraindications or unavailability. Low-field (LF) MRI (<0.5T) can detect several types of brain injury, including ischaemic and haemorrhagic stroke. Implementing LF-MRI in acute stroke care may offer several advantages, including extended applicability, increased safety, faster administration, reduced staffing and costs. This multicentric prospective open-label trial aims to evaluate the diagnostic accuracy of LF-MRI, as a tool to guide treatment decision in acute stroke. METHODS AND ANALYSIS: Consecutive patients accessing the emergency department with suspected stroke dispatch will be recruited at three Italian study units: Azienda Sanitaria Locale (ASL) Abruzzo 1 and 2, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital. The estimated sample size is 300 patients. Anonymised clinical and LF-MRI data, along with conventional neuroimaging data, will be independently assessed by two external units: Marche Polytechnic University and 'G. Martino' Polyclinic University Hospital. Both units will independently adjudicate the best treatment option, while the latter will provide historical HF-MRI data to develop artificial intelligence algorithms for LF-MRI images interpretation (Free University of Bozen-Bolzano). Agreement with conventional neuroimaging will be evaluated at different time points: hyperacute, acute (24 hours), subacute (72 hours), at discharge and chronic (4 weeks). Further investigations will include feasibility study to develop a mobile stroke unit equipped with LF-MRI and cost-effectiveness analysis. This trial will provide necessary data to validate the use of LF-MRI in acute stroke care. ETHICS AND DISSEMINATION: The study was approved by the Research Ethics Committee of the Abruzzo Region (CEtRA) on 11 May 2023 (approval code: richyvgrg). Results will be disseminated in peer-reviewed journals and presented in academic conferences. TRIAL REGISTRATION NUMBER: NCT05816213; Pre-Results.

Effect of General Anesthesia Versus Conscious Sedation/Local Anesthesia on the Outcome of Patients with Minor Stroke and Isolated M2 Occlusion Undergoing Immediate Thrombectomy: A Retrospective Multicenter Matched Analysis.

BACKGROUND: This study investigates the impact of general anesthesia (GA) versus conscious sedation/local anesthesia (CS/LA) on the outcome of patients with minor stroke and isolated M2 occlusion undergoing immediate mechanical thrombectomy (iMT). METHODS: The databases of 16 comprehensive stroke centers were retrospectively screened for consecutive patients with isolated M2 occlusion and a baseline National Institutes of Health Stroke Scale score ≤5 who received iMT. Propensity score matching was used to estimate the effect of GA versus CS/LA on clinical outcomes and procedure-related adverse events. The primary outcome measure was a 90-day modified Rankin Scale (mRS) score of 0-1. Secondary outcome measures were a 90-day mRS score of 0-2 and all-cause mortality, successful reperfusion, procedural-related symptomatic subarachnoid hemorrhage, intraprocedural dissections, and new territory embolism. RESULTS: Of the 172 patients who were selected, 55 received GA and 117 CS/LA. After propensity score matching, 47 pairs of patients were available for analysis. We found no significant differences in clinical outcome, rates of efficient reperfusion, and procedural-related complications between patients receiving GA or LA/CS (mRS score 0-1, P = 0.815; mRS score 0-2, P = 0.401; all-cause mortality, P = 0.408; modified Treatment in Cerebral Infarction score 2b-3, P = 0.374; symptomatic subarachnoid hemorrhage, P = 0.082; intraprocedural dissection, P = 0.408; new territory embolism, P = 0.462). CONCLUSIONS: In patients with minor stroke and isolated M2 occlusion undergoing iMT, the type of anesthesia does not affect clinical outcome or the rate of procedural-related complications. Our results agree with recent data showing no benefit of one specific anesthesiologic procedure over the other and confirm their generalizability also to patients with minor baseline symptoms.

Predictors of parenchymal hematoma and clinical outcome after mechanical thrombectomy in patients with large ischemic core due to large vessel occlusion: a retrospective multicenter study.

BACKGROUND: The aim of our study was to find predictors of parenchymal hematoma (PH) and clinical outcome after mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) and baseline large infarct. METHODS: The databases of 16 stroke centers were retrospectively screened for patients with anterior circulation LVO and baseline Alberta Stroke Program Early CT Score (ASPECTS) ≤5 that received MT. Procedural parameters, including the number of passes during first and second technique of MT, were recorded. Outcome measures were occurrence of PH type 2 and any type of PH after MT, and the 90-day modified Rankin Scale (mRS) score of 0-3 and 0-2. RESULTS: In total, 408 patients were available for analysis. A higher number of passes in the second technique was predictive of PH type 2 (odds ratio (OR) - 3.204, 95% confidence interval (CI) 1.140 to 9.005), whereas procedure conducted under general anesthesia was associated with lower risk (OR 0.127, 95% CI 0.002 to 0.808). The modified thrombolysis in cerebral infarction grade 2c-3 was associated with the mRS score 0-3 (OR 3.373, 95% CI 1.891 to 6.017), whereas occurrence of PH type 2 was predictive of unfavorable outcome (OR 0.221, 95% CI 0.063 to 0.773). Similar results were found for the mRS score 0-2 outcome measure. CONCLUSION: In patients with large ischemic core, a higher number of passes during MT and procedure not conducted under general anesthesia are associated with increased rate of PH type 2, that negatively impact the clinical outcome. Our data outline a delicate balance between the need of a complete recanalization and the risk of PH following MT.

Factors associated with hemorrhagic transformation after endovascular treatment despite early recanalization.

PURPOSE: To identify new factors associated with hemorrhagic transformation (HT) despite early recanalization in patients with acute ischemic stroke treated with mechanical thrombectomy. METHODS: We retrospectively included patients with known onset of large vessel occlusion treated with mechanical thrombectomy +/- intravenous thrombolysis. Non-contrast CT was performed at 24 +/- 12 h from endovascular procedure. We collected data on patient characteristics, risk factors, radiological and treatment features, stroke severity on admission and discharge, carotid intima-media thickness (CIMT), Neutrophils-to-Lymphocytes ratio (NLR), white matter hyperintensities measured according to the Fazekas score on FLAIR MRI data. The main outcome measures were the incidence of HT and factors associated with it. Secondary outcome measures were symptomatic intracerebral hemorrhage and parenchymal hematoma. RESULTS: Of 874 patients, 472 met the inclusion criteria, 211 (44.7%) had HT. Factors significantly associated with increased risk of HT included onset-to-recanalization time, CIMT (normal/mild), ASPECT-MRI < 6, and a higher NLR. We found that beyond 7.67 h from onset-to-recanalization, the risk of HT increases and exceeds 50%. ASPECT-MRI, NLR, and CIMT independently predict HT despite early recanalization. CONCLUSIONS: We identified novel factors associated with HT in patients with acute ischemic stroke of known onset treated with mechanical thrombectomy. We found that at 7.67 h from onset to recanalization, the risk of HT is >50%, and we identified factors responsible for HT despite early recanalization.

Mechanical thrombectomy in young patients with large vessel occlusion-related ischemic stroke: Data from the Italian Registry of Endovascular Treatment in Acute Stroke.

BACKGROUND AND PURPOSE: The weight of outcome predictors in acute ischemic stroke (AIS) patients older than 60 years is not necessarily mirrored in the younger population, posing the question of whether outcome determinants specific for the latter might vary. Very few data are available on predictors of outcome in young AIS patients receiving endovascular treatment (EVT). METHODS: We analyzed data for patients aged between 16 and 55 years from the Italian Registry of Endovascular Treatment in Acute Stroke. We divided our population into patients <45 years old and patients aged between 45 and 55 years. After testing the differences between groups in terms of 90-day modified Rankin Scale (mRS) 0-2, mortality, and symptomatic intracranial hemorrhage, we looked for predictors of poor outcome (mRS 3-6), death, and symptomatic intracerebral hemorrhage in the two groups. RESULTS: A total of 438 patients younger than 45 years and 817 aged 45-55 years were included; 284 (34.8%) patients aged 45-55 years and 112 (25.6%) patients younger than 45 years old showed poor 90-day functional outcome (p = 0.001). Predictors of poor outcome in the older group were baseline National Institutes of Health Stroke Scale (NIHSS; p < 0.001), diabetes (p = 0.027), poor collateral status (p = 0.036), and groin puncture-to-recanalization time (p = 0.010), whereas Thrombolysis in Cerebral Infarction (TICI) 2b-3 had an inverse association (p < 0.001). Predictors of poor outcome in patients younger than 45 years were baseline NIHSS (p < 0.001) and groin puncture-to-recanalization time (p = 0.015), whereas an inverse association was found for baseline Alberta Stroke Program Early CT Score (p = 0.010) and TICI 2b-3 (p < 0.001). CONCLUSIONS: Approximately one third of young adults treated with EVT do not reach a good functional outcome. Fast and successful recanalization, rather than common risk factors, has a major role in determining clinical outcome.

Predictors for hemorrhagic transformation and cerebral edema in stroke patients with first-pass complete recanalization.

BACKGROUND: Predictors of radiological complications attributable to reperfusion injury remain unknown when baseline setting is optimal for endovascular treatment and procedural setting is the best in stroke patients with large vessel occlusion (LVO). AIMS: To identify clinical and radiological/procedural predictors for hemorrhagic transformation (HT) and cerebral edema (CED) at 24 hr in patients obtaining complete recanalization in one pass of thrombectomy for ischemic stroke ⩽ 6 h from symptom onset with intra-cranial anterior circulation LVO and ASPECTS ⩾ 6. METHODS: We conducted a cohort study on prospectively collected data from 1400 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. RESULTS: HT was reported in 248 (18%) patients and early CED was reported in 260 (19.2%) patients. In the logistic regression model including predictors from a first model with clinical variables and from a second model with radiological/procedural variables, diabetes mellitus (odds ratio (OR) = 1.832, 95% confidence interval (CI) = 1.201-2.795), higher National Institutes of Health Stroke Scale (NIHSS) (OR = 1.076, 95% CI = 1.044-1.110), lower Alberta Stroke Program Early CT (ASPECTS) (OR = 0.815, 95% CI = 0.694-0.957), and longer onset-to-groin time (OR = 1.005, 95% CI = 1.002-1.007) were predictors of HT, whereas general anesthesia was inversely associated with HT (OR = 0.540, 95% CI = 0.355-0.820). Higher NIHSS (OR = 1.049, 95% CI = 1.021-1.077), lower ASPECTS (OR = 0.700, 95% CI = 0.613-0.801), intravenous thrombolysis (OR = 1.464, 95% CI = 1.061-2.020), longer onset-to-groin time (OR = 1.002, 95% CI = 1.001-1.005), and longer procedure time (OR = 1.009, 95% CI = 1.004-1.015) were predictors of early CED. After repeating a fourth logistic regression model including also good collaterals, the same variables remained predictors for HT and/or early CED, except diabetes mellitus and thrombolysis, while good collaterals were inversely associated with early CED (OR = 0.385, 95% CI = 0.248-0.599). CONCLUSIONS: Higher NIHSS, lower ASPECTS, and longer onset-to-groin time were predictors for both HT and early CED. General anesthesia and good collaterals were inversely associated with HT and early CED, respectively. Longer procedure time was predictor of early CED.

Mechanical thrombectomy in patients with heart failure: the Italian registry of Endovascular Treatment in Acute Stroke.

BACKGROUND: Heart failure (HF) is the second most important cardiac risk factor for stroke after atrial fibrillation (AF). Few data are available on mechanical thrombectomy (MT) in acute ischemic stroke (AIS) patients with HF. METHODS: The source of data is the multicentre Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS). All AIS patients ≥ 18 years receiving MT were categorised in two groups: HF and no-HF. Baseline clinical and neuroradiological findings on admission were analysed. RESULTS: Of 8924 patients, 642 (7.2%) had HF. Compared to the no-HF group, HF patients had higher prevalence of cardiovascular risk factors. Rate of complete recanalisation (TICI 2b-3) was 76.9% in HF vs 78.1% in no-HF group (p = 0.481). Rate of symptomatic intracerebral haemorrhage at 24-h non-contrast computed tomography (NCCT) was 7.6% in HF vs 8.3% in no-HF patients (p = 0.520). At 3 months, 36.4% of HF patients and 48.2% of no-HF patients (p < 0.001) had mRS 0-2, and mortality was, respectively, 30.7% and 18.5% (p < 0.001). In multivariate logistic regression, HF was independently associated with mortality at 3 months (OR 1.53, 1.24-1.88 95% CI, p < 0.001). In multivariate ordinal regression, HF patients had a probability of transitioning to a higher mRS level of 1.23 (1.05-1.44 95% CI, p = 0.012). The propensity score analysis of two groups matched for age, sex, and NIHSS at admission yielded the same results. CONCLUSION: MT is safe and effective in HF patients with AIS. Patients with HF and AIS suffered from higher 3-month mortality and unfavourable outcome regardless of acute treatments.

Early neurological deterioration in patients with minor stroke due to isolated M2 occlusion undergoing medical management: a retrospective multicenter study.

BACKGROUND: Patients with minor stroke and M2 occlusion undergoing best medical management (BMM) may face early neurological deterioration (END) that can lead to poor long-term outcome. In case of END, rescue mechanical thrombectomy (rMT) seems beneficial. Our study aimed to define factors relevant to clinical outcome in patients undergoing BMM with the possibility of rMT on END, and find predictors of END. METHODS: Patients with M2 occlusion and a baseline National Institutes of Health Stroke Scale (NIHSS) score≤5 that received either BMM only or rMT on END after BMM were extracted from the databases of 16 comprehensive stroke centers. Clinical outcome measures were a 90-day modified Rankin Scale (mRS) score of 0-1 or 0-2, and occurrence of END. RESULTS: Among 10 169 consecutive patients with large vessel occlusion admitted between 2016 and 2021, 208 patients were available for analysis. END was reported in 87 patients that were therefore all subjected to rMT. In a logistic regression model, END (OR 3.386, 95% CI 1.428 to 8.032), baseline NIHSS score (OR 1.362, 95% CI 1.004 to 1.848) and a pre-event mRS score=1 (OR 3.226, 95% CI 1.229 to 8.465) were associated with unfavorable outcome. In patients with END, successful rMT was associated with favorable outcome (OR 4.549, 95% CI 1.098 to 18.851). Among baseline clinical and neuroradiological features, presence of atrial fibrillation was a predictor of END (OR 3.547, 95% CI 1.014 to 12.406). CONCLUSION: Patients with minor stroke due to M2 occlusion and atrial fibrillation should be closely monitored for possible worsening during BMM and, in this case, promptly considered for rMT.

Flow Diverting Stents in Cerebral Small Caliber Vessels (< 2 mm) for Aneurysm Treatment : A Three Center Retrospective Study.

PURPOSE: The off-label use of flow diverting stents (FDS) for treating cerebral aneurysms in small distal vessels is increasing in clinical practice with encouraging results; however, data directly addressing the parent vessel size are still scarce. Our aim was to evaluate the safety and efficacy of FDS placement in anterior and posterior circulation aneurysms with parent arteries ≤ 2 mm in a real-world representative setting. METHODS: We retrospectively reviewed patients treated with FDS at the three participating university hospitals between 2009 and 2021. The inclusion criteria were the placement of at least one FDS in a parent vessel with a maximum diameter of 2 mm or less. The primary clinical safety endpoint was the absence of death, major or minor symptomatic stroke, transient ischemic attack and procedure-related intracranial hemorrhage. Clinical outcome was assessed using the modified Rankin Scale (mRS) score at the follow-up visit at 1 year. The primary efficacy endpoint was defined as complete and near-complete occlusion at the 1­year follow-up. RESULTS: We identified 55 patients harboring 56 aneurysms. The primary clinical safety endpoint was obtained in 93% of cases. The hemorrhagic and thromboembolic complication rates were 4% and 9%, respectively. No patient died or had a relevant discrepancy (> 1 point) at the pre-mRS and post-mRS. The primary efficacy endpoint was reached in 80% of cases. CONCLUSION: The use of FDS in vessels < 2 mm is technically feasible with good aneurysm occlusion rates and an acceptable safety profile. Nevertheless, it is essential to be aware of the of the main complications associated when operating in small diameter vessels.

Comparison between second generation HydroSoft coils and bare platinum coils for the treatment of large intracranial aneurysms.

BACKGROUND: The development of HydroSoft coils (HSC) aims to reduce the high recurrence and retreatment rates observed in large brain aneurysms by improving primary brain aneurysm filling and thus occlusion efficacy. We compared clinical and angiographic effectiveness of bare platinum coils (BPC) versus second generation HSC for large intracranial aneurysms at our center. METHODS: We included 61 large aneurysms between 2015 and 2018, 29 embolized primarily using HSC and 32 treated with BPC. The aneurysm occlusion rates were assessed after 3 and 12 months with an MRI scan and at 6 moths with a control digital subtraction angiography (DSA) using the Raymond-Roy occlusion classification (RROC). Clinical outcomes were evaluated using the modified ranking scale (mRS). RESULTS: The observed immediate occlusion rate was slightly better in the BPC group, however, this group had a significant increase of progressive reperfusion at all imaging follow-up. Contrarily, the rate of complete occlusion increased significantly in the HSC group, starting from the 6 and 12-months follow-up. 7 aneurysms (11.4%) were re-treated (15.6% BPC and 6.9% HSC). The 6 and 12-months clinical data showed mRS score 0-1 in 96.7% of patients. CONCLUSIONS: In our single-center experience, the second generation HydroSoft coils were shown to be safe and effective for endovascular treatment of large intracranial aneurysms with encouraging clinical and angiographic results, also for ruptured aneurysms. Even if the validity is limited due to our small cohort size, HSC showed a significantly lower rate of recurrence at mid-term follow-up when compared to BPC.

Mechanical thrombectomy in minor stroke due to isolated M2 occlusion: a multicenter retrospective matched analysis.

BACKGROUND: The purpose of this study was to evaluate the effectiveness of mechanical thrombectomy (MT) in patients with isolated M2 occlusion and minor symptoms and identify possible baseline predictors of clinical outcome. METHODS: The databases of 16 high-volume stroke centers were retrospectively screened for consecutive patients with isolated M2 occlusion and a baseline National Institutes of Health Stroke Scale (NIHSS) score ≤5 who received either early MT (eMT) or best medical management (BMM) with the possibility of rescue MT (rMT) on early neurological worsening. Because our patients were not randomized, we used propensity score matching (PSM) to estimate the treatment effect of eMT compared with the BMM/rMT. The primary clinical outcome measure was a 90-day modified Rankin Scale score of 0-1. RESULTS: 388 patients were initially selected and, after PSM, 100 pairs of patients receiving eMT or BMM/rMT were available for analysis. We found no significant differences in clinical outcome and in safety measures between patients receiving eMT or BMM/rMT. Similar results were also observed after comparison between eMT and rMT. Concerning baseline predicting factors of outcome, the involvement of the M2 inferior branch was associated with a favorable outcome. CONCLUSION: Our multicenter retrospective analysis has shown no benefit of eMT in minor stroke patients with isolated M2 occlusion over a more conservative therapeutic approach. Although our results must be viewed with caution, in these patients it appears reasonable to consider BMM as the first option and rMT in the presence of early neurological deterioration.

Three-Dimensional Constructive Interference in Steady State (3D CISS) Imaging and Clinical Applications in Brain Pathology.

Three-dimensional constructive interference in steady state (3D CISS) is a steady-state gradient-echo sequence in magnetic resonance imaging (MRI) that has been used in an increasing number of applications in the study of brain disease in recent years. Owing to the very high spatial resolution, the strong hyperintensity of the cerebrospinal fluid signal and the high contrast-to-noise ratio, 3D CISS can be employed in a wide range of scenarios, ranging from the traditional study of cranial nerves, the ventricular system, the subarachnoid cisterns and related pathology to more recently discussed applications, such as the fundamental role it can assume in the setting of acute ischemic stroke, vascular malformations, infections and several brain tumors. In this review, after briefly summarizing its fundamental physical principles, we examine in detail the various applications of 3D CISS in brain imaging, providing numerous representative cases, so as to help radiologists improve its use in imaging protocols in daily clinical practice.

Deciphering impact of single nucleotide polymorphisms on cotranscriptional modification in CCM gene mRNAs.

Novel insights on regulation of gene expression mechanisms highlight the pivotal role of epitranscriptomic modifications on decision about transcript fate. These modifications include methylation of adenosine and cytosine in RNA molecules. Impairment of the normal epitranscriptome profile was observed in several pathological conditions, such as cancer and neurodegeneration. However, it is still unknown if alteration of this regulatory mechanism can be involved in cerebral cavernous malformation (CCM) development. CCM is a rare genetic condition affecting brain microvasculature, resulting from mutations in the three genes KRIT1, CCM2, and PDCD10. By data integration of association study, in silico prediction, and gene expression analysis, we evaluated role of single nucleotide polymorphisms (SNPs) highly recurrent in patients with CCM, on CCM gene expression regulation. Results showed that several of these SNPs lead to a drastic downexpression, in KRIT1 and CCM2 genes and this downregulation can be due to alteration of epitranscriptome profile, occurring these SNPs in gene regions that are subject to epitranscriptome modifications. These data suggest that this novel mechanism of gene expression regulation can be consider to further investigation on CCM pathogenesis.

Image-guided robotic radiosurgery for the treatment of arteriovenous malformations.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) are challenging lesions, often requiring multimodal interventions; however, data on the efficacy of stereotactic radiosurgery for cerebral AVMs are limited. This study aimed to evaluate the clinical and radiographic results following robotic radiosurgery, alone or in combination with endovascular treatment, and to investigate factors associated with obliteration and complications in patients with AVM. METHODS: We retrospectively analyzed the clinical and imaging characteristics of 123 patients with AVMs of all Spetzler-Martin grades treated at two institutions by robotic radiosurgery in single-fraction doses (CyberKnife). Embolization was performed before radiosurgery in a subset of patients to attempt to downgrade the lesions. Factors associated with AVM obliteration and complications (toxicity) were identified via univariate and multivariate analyses. RESULTS: The median follow-up time was 48.1 months (range, 3.6-123 months). Five patients were lost to follow-up. The obliteration rate in the 59 patients with a follow-up period exceeding four years was 72.8%. Complete obliteration and partial remission were achieved in 67 (56.8%) and 31 (26.3%) cases, respectively, whereas no change was observed in 20 cases (17.8%). Embolization was performed in 54/123 cases (43.9%). Complete and partial obliteration were achieved in 29 (55.7%) and 14 (26.9%) embolized patients, respectively. In the multivariate analysis, the factors associated with obliteration were age (p = .018) and the Spetzler-Martin grade (p = .041). Treatment-induced toxicity (radiation necrosis and/or edema) was observed in 15 cases (12.7%), rebleeding occurred in three cases (2.5%), and the rate of mortality associated with rebleeding was 1.7%. CONCLUSIONS: CyberKnife radiosurgery is a valid approach for treating AVMs of all Spetzler-Martin-grades, with satisfactory obliteration rates, low toxicity, and a relatively rare incidence of rebleeding.

Magnetic Resonance Angiography and Cisternography fused images in acute ischemic stroke may save time during endovascular procedure revealing vessel anatomy.

Background and purpose: Endovascular treatment (EVT) is a time-dependent procedure that aims to remove the arterial blood flow obstruction in brain vessels in acute ischemic stroke. In our center, the MRI patient selection protocol in acute ischemic stroke is performed with DWI, FLAIR, MR angiography (MRA) and MR cisternography (MRC) sequences. MRA and MRC are promptly and automatically fused in order to have a clear detection of vessel anatomy, before and during EVT.Our study aim is to evaluate if the fusion process between MRA and MRC could be considered time-safe and could influence EVT duration or outcome. Materials and methods: 45 patients were retrospectively selected for the study and divided into 2 groups according to the presence of MRC sequence fused with MRA (Group 1) or not (Group 2 - controls). Results: MRA and MRC fusion was able to depict vessel anatomy in all subjects of Group 1 (22 patients, 12 females; age 75.59 years ± 10.87). Group 1 presented EVT time reduction (p < 0.05; p = 0.040) (51.59 min ± 30.94) when compared to Group 2 (23 patients, 13 females; age 75.04 years ± 12.12) (71.96 min ± 34.55) of 20.37 min average. No differences between groups were detected evaluating: NIHSS at admission (p = 0.49) and discharge (p = 0.67), pre-stroke mRS (p = 0.89), mRS at 90 days (p = 0.62), ASPECT (p = 0.98) and ASPECT-DWI scores (p = 0.93), time from symptom onset to groin puncture (p = 0.80), thromboaspiration vs combined technique (p = 0.67), EVT success (p = 0.63). Conclusion: Fusion of MRA and MRC is a safe and promising technique in promptly revealing vascular anatomy beyond vessel obstruction, and can play a role in EVT duration reduction.

Carotid free-floating thrombus during COVID-19 vaccine era: causality or not?

Carotid free-floating thrombus (FFT) is very rarely diagnosed in patients with acute ischemic stroke. It is a real clinical emergency due to the significant risk of death associated with thromboembolic complications. Herein, we present three patients with ischemic stroke caused by carotid FFT after less than 20 days from administration of mRNA vaccine BNT162b1 (Pfizer/BioNTech) for Severe Acute Respiratory Syndrome-CoronaVirus 2 (SARS-CoV-2). To our knowledge, these are the first cases reporting carotid FTT following SARS-CoV-2 vaccination.