Association between procedural time and outcome in unsuccessful mechanical thrombectomy for acute ischemic stroke: analysis from the Italian Registry of Endovascular Treatment in Acute Stroke.

BACKGROUND: We aim to assess the association between procedural time and outcomes in patients in unsuccessful mechanical thrombectomy (MT) for anterior circulation acute stroke. METHODS: We conducted a cohort study on prospectively collected data from patients with M1 and/or M2 segment of middle cerebral artery occlusion with a thrombolysis in cerebral infarction 0-1 at the end of procedure. Primary outcome was 90-day poor outcome. Secondary outcomes were early neurological deterioration (END), symptomatic intracranial hemorrhage (sICH) according to ECASS II and sICH according to SITS-MOST. RESULTS: Among 852 patients, after comparing characteristics of favourable and poor outcome groups, logistic regression analysis showed age (OR: 1.04; 95%CI: 1.02-1.05; p < 0.001), previous TIA/stroke (OR: 0.23; 95%CI: 0.12-0.74; p = 0.009), M1 occlusion (OR: 1.69; 95%CI: 1.13-2.50; p = 0.01), baseline NIHSS (OR: 1.01; 95%CI: 1.06-1.13; p < 0.001) and procedural time (OR:1.00; 95% CI: 1.00-1.01; p = 0.003) as independent predictors poor outcome at 90 days. Concerning secondary outcomes, logistic regression analysis showed NIHSS (OR:0.96; 95%CI: 0.93-0.99; p = 0.008), general anaesthesia (OR:2.59; 95%CI: 1.52-4.40; p < 0.001), procedural time (OR: 1.00; 95% CI: 1.00-1.01; p = 0.002) and intraprocedural complications (OR: 1.89; 95%CI: 1.02-3.52; p = 0.04) as independent predictors of END. Bridging therapy (OR:2.93; 95%CI: 1.21-7.09; p = 0.017) was associated with sICH per SITS-MOST criteria whereas M1 occlusion (OR: 0.35; 95%CI: 0.18-0.69; p = 0.002), bridging therapy (OR: 2.02; 95%CI: 1.07-3.82; p = 0.03) and intraprocedural complications (OR: 5.55; 95%CI: 2.72-11.31; p < 0.001) were independently associated with sICH per ECASS II criteria. No significant association was found between the number of MT attempts and analyzed outcomes. CONCLUSIONS: Regardless of the number of MT attempts and intraprocedural complications, procedural time was associated with poor outcome and END. We suggest a deeper consideration of procedural time when treating anterior circulation occlusions refractory to MT.

Endovascular treatment of acute arteriosclerotic vertebrobasilar occlusion: A single center experience.

OBJECTIVES: Few experiences on vertebrobasilar occlusion over underlying intracranial atherosclerotic disease have been reported in literature and the optimal strategy on how to perform a mechanical thrombectomy is unclear. The aim of this paper is to bring our experience based on patients admitted with acute vertebrobasilar occlusion with underlying atheromatous lesions. MATERIALS AND METHODS: Several data were collected from August 2009 to October 2022 including clinical history, pre- and post-treatment neurological objectivity, diagnostic images and angiographic procedural images, and clinical outcome at 6 months. We selected 13 patients from August 2009 to October 2022, 12 men and 1 woman, aged 40 to 82 years (mean age, 62.6 years). RESULTS: Mechanical thrombectomy with a thromboaspiration was performed in all patients as beginning of the procedure. In three patients, the procedures resulted in excellent angiographic result and clinical outcome, while in three patients, we observed a failure of the procedural and clinical outcome. For residual intracranial stenosis in three patients, an angioplasty was performed obtaining an ischemic area related to the posterior circulation. In four patients, a stent was placed, in three patients, we obtained a good clinical outcome with a mRS between 0 and 2, while one treatment resulted in death, probably due to a late endovascular treatment. CONCLUSIONS: Endovascular treatment with stent deployment appears to result in an excellent outcome in patients with occlusion of the vertebrobasilar circulation in cases of occlusion on atheromatic plaque. The degree of residual stenosis after thrombospiration can significantly affect subsequent type of treatment.

Aspiration thrombectomy of M2 segment in acute ischemic stroke: The clinical reality in a neurovascular reference center.

OBJECTIVE: Our study aimed to evaluate safety, efficacy and clinical outcomes in patients with acute ischemic stroke with occlusion of M2 segment treated with thromboaspiration. MATERIALS AND METHODS: A retrospective study was conducted in patients with ischemic stroke of M2 segment undergoing endovascular thromboaspiration. The time period analyzed was from October 2015 until February 2021. Thromboaspiration was performed with AXS Catalyst 5 (Stryker) or AXS Catalyst 6 (Stryker) catheters. The following parameters were assessed: risk factors for ischemic stroke, National Institutes of Health Stroke Scale (entry and discharge), pre-procedural fibrinolysis, pre-procedural and 24-h Alberta Stroke Program Early CT Score, recanalization time, number of passages for recanalization, Thrombolysis in cerebral infarction scale score, periprocedural complications, Modified Rankin Scale score at 90 days from procedure and mortality. RESULTS: 90 patients were included in the study. The mean age was 75 ± 11.1 with National Institutes of Health Stroke Scale at entry 13 ± 5 and 8 ± 4 at discharge. Pre-procedural fibrinolysis were performed in 40 patients. Pre-procedural Alberta Stroke Program Early CT Score were 8.8 ± 1.3 and 6.9 ± 2.4 after 24 h from the procedure. Time of recanalization from onset of symptoms was 300 ± 82 min. Number of passages for recanalization were 1.8 ± 1.1. Thrombolysis in cerebral infarction scale score ≥ 2b were obtained in 90 % of procedures. After 90 days 33 % of patient obtained an Modified Rankin Scale between 0 and 1 (between 0 and 2 was 40 %). We didn't detect any complication in 64 % of cases (subarachnoid haemorrhage in 2 %, HI1 and HI 2 in 15 %, PH1 in 9 % of patients, PH2 in 6 % of patients). CONCLUSIONS: This paper confirms the usefulness and safety of thrombospiration in patients with ischemic stroke in the M2 segment with low intra-operative risks, high technical success and positive impact on the outcome of the patients.

CT Perfusion as a Predictor of the Final Infarct Volume in Patients with Tandem Occlusion.

BACKGROUND: CT perfusion (CTP) is used in patients with anterior circulation acute ischemic stroke (AIS) for predicting the final infarct volume (FIV). Tandem occlusion (TO), involving both intracranial large vessels and the ipsilateral cervical internal carotid artery could generate hemodynamic changes altering perfusion parameters. Our aim is to evaluate the accuracy of CTP in the prediction of the FIV in TOs. METHODS: consecutive patients with AIS due to middle cerebral artery occlusion, referred to a tertiary stroke center between March 2019 and January 2021, with an automated CTP and successful recanalization (mTICI = 2b - 3) after endovascular treatment were retrospectively included in the tandem group (TG) or in the control group (CG). Patients with parenchymal hematoma type 2, according to ECASS II classification of hemorrhagic transformations, were excluded in a secondary analysis. Demographic, clinical, radiological, time intervals, safety, and outcome measures were collected. RESULTS: among 319 patients analyzed, a comparison between the TG (N = 22) and CG (n = 37) revealed similar cerebral blood flow (CBF) > 30% (29.50 ± 32.33 vs. 15.76 ± 20.93 p = 0.18) and FIV (54.67 ± 65.73 vs. 55.14 ± 64.64 p = 0.875). Predicted ischemic core (PIC) and FIV correlated in both TG (tau = 0.761, p < 0.001) and CG (tau = 0.315, p = 0.029). The Bland-Altmann plot showed agreement between PIC and FIV for both groups, mainly in the secondary analysis. CONCLUSION: automated CTP could represent a good predictor of FIV in patients with AIS due to TO.

Temporal lobe atrophy as a potential predictor of functional outcome in older adults with acute ischemic stroke.

BACKGROUND: To explore whether temporal lobe atrophy predicts 3-month functional outcome in a population of patients with anterior circulation acute ischemic stroke (AIS) treated with mechanical thrombectomy (MT). METHODS: We retrospectively selected patients > 65 years from our prospective endovascular stroke registry between June 2013 and August 2018. According to 3-month modified Rankin Scale (mRS), patients were divided in two groups, named good (mRS ≤ 2) and poor (mRS > 2) outcome. Measures of temporal lobe atrophy (i.e., interuncal distance [IUD], medial temporal lobe thickness [mTLT] and radial width of temporal horn [rWTH]) were assessed on pre-treatment CT scan. Cutoff values for good outcome were obtained for IUD, mTLT and rWTH by means of non-parametric ROC curve analysis. Multivariate analysis was performed to identify predictors of outcome. Ordinal shift analysis based on cutoff values was built to evaluate differences in 3-month mRS. RESULTS: Among 340 patients, 130 (38.2%) had good and 210 (61.8%) had poor outcome. We found the following cutoff values for good outcome: < 25 mm for IUD, > 15 mm for mTLT and < 4 mm for rWTH. Lower IUD (OR 0.71; 95% CI 0.63-0.80; p < 0.0001) and rWTH (OR 0.73; 95% CI 0.61-0.87; p < 0.0001) and higher mTLT (OR 1.30; 95% CI 1.14-1.49; p < 0.0001) were independently associated with good outcome. Ordinal shift analysis based on cutoff values revealed significant differences in the rate of good outcome for rWTH (49 vs 27%; p < 0.0001), mTLT (52 vs 21%; p < 0.0001) and IUD (57 vs 17%; p < 0.0001). CONCLUSIONS: Assessment of temporal lobe atrophy may predict functional outcome in patients with AIS treated with MT.

Can machine learning of post-procedural cone-beam CT images in acute ischemic stroke improve the detection of 24-h hemorrhagic transformation? A preliminary study.

PURPOSE: Hemorrhagic transformation (HT) is an independent predictor of unfavorable outcome in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT). Its early identification could help tailor AIS management. We hypothesize that machine learning (ML) applied to cone-beam computed tomography (CB-CT), immediately after EVT, improves performance in 24-h HT prediction. METHODS: We prospectively enrolled AIS patients undergoing EVT, post-procedural CB-CT, and 24-h non-contrast CT (NCCT). Three raters independently analyzed imaging at four anatomic levels qualitatively and quantitatively selecting a region of interest (ROI) < 5 mm2. Each ROI was labeled as "hemorrhagic" or "non-hemorrhagic" depending on 24-h NCCT. For each level of CB-CT, Mean Hounsfield Unit (HU), minimum HU, maximum HU, and signal- and contrast-to-noise ratios were calculated, and the differential HU-ROI value was compared between both hemispheres. The number of anatomic levels affected was computed for lesion volume estimation. ML with the best validation performance for 24-h HT prediction was selected. RESULTS: One hundred seventy-two ROIs from affected hemispheres of 43 patients were extracted. Ninety-two ROIs were classified as unremarkable, whereas 5 as parenchymal contrast staining, 29 as ischemia, 7 as subarachnoid hemorrhages, and 39 as HT. The Bernoulli Naïve Bayes was the best ML classifier with a good performance for 24-h HT prediction (sensitivity = 1.00; specificity = 0.75; accuracy = 0.82), though precision was 0.60. CONCLUSION: ML demonstrates high-sensitivity but low-accuracy 24-h HT prediction in AIS. The automated CB-CT imaging evaluation resizes sensitivity, specificity, and accuracy rates of visual interpretation reported in the literature so far. A standardized quantitative interpretation of CB-CT may be warranted to overcome the inter-operator variability.

Carotid artery stenting during endovascular thrombectomy for acute ischemic stroke with tandem occlusion: the Italian Registry of Endovascular Treatment in Acute Stroke.

PURPOSE: The management of tandem extracranial internal carotid artery and intracranial large vessel occlusion during endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) has been under-investigated. We sought to investigate outcomes of AIS patients with tandem occlusion (TO) treated with carotid artery stenting (CAS) compared to those not treated with CAS (no-CAS) during EVT. METHODS: We performed a cohort study using data from AIS patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. Outcomes were 3 months' mortality, functional outcome, complete and successful recanalization, any intracranial hemorrhage, parenchymal hematoma and symptomatic intracerebral hemorrhage. RESULTS: Among 466 AIS patients with TO, CAS patients were 122 and no-CAS patients were 226 (118 excluded). After adjustment for unbalanced variables, CAS was associated with a lower rate of 3 months' mortality (OR 0.407, 95% CI 0.171-0.969, p = 0.042). After adjustment for pre-defined variables, CAS was associated with a lower rate of 3 months' mortality (aOR 0.430, 95% CI 0.187-0.989, p = 0.047) and a higher rate of complete recanalization (aOR 1.986, 95% CI 1.121-3.518, p = 0.019), successful recanalization (aOR 2.433, 95% CI 1.263-4.686, p = 0.008) and parenchymal hematoma (aOR 2.876, 95% CI 1.173-7.050, p = 0.021). CAS was associated with lower 3 months mortality (OR 0.373, 95% CI 0.141-0.982, p = 0.046) and higher rates of successful recanalization (OR 2.082, 95% CI 1.099-3.942, p = 0.024) after adjustment for variables associated with 3 months' mortality and successful recanalization, respectively. CONCLUSIONS: Among AIS patients with TO, CAS during EVT was associated with a higher rate of successful reperfusion and a lower rate of 3 months' mortality.

Diabetes mellitus contributes to higher cerebrospinal fluid tau levels selectively in Alzheimer's disease patients with the APOE4 genotype.

BACKGROUND AND PURPOSE: Diabetes mellitus (DM) is considered a risk factor for Alzheimer's disease (AD) and shares some pathological pathways, such as activation of amyloid cascade and tau phosphorylation. The aim of the present study was to investigate to what extent DM could impact on neurodegeneration within the AD continuum, using ß amyloid (A: Aß1-42 ) and phosphorylated tau (T: p-tau) biomarkers to discriminate patients by Alzheimer's pathological change (A+/T-) and AD (A+/T+), according to the National Institute on Aging and Alzheimer's Association classification. In addition, we aimed to evaluate whether APOE genotype interacts with tau protein and glucose metabolism dysfunction to affect the pathological process. METHODS: For this retrospective observational study, 1350 patients were recruited. The patients underwent a complete clinical investigation, neuropsychological assessment, lumbar puncture for cerebrospinal fluid (CSF) biomarkers analysis and APOE genotyping. RESULTS: A total of 607 patients fulfilled the clinical criteria of mild cognitive impairment or early dementia. In A+T- patients (n = 350), DM did not influence CSF biomarker levels, while among A+T+ patients (n = 257) those with DM showed increased total tau (t-tau) levels compared to non-DM patients (DM: 919.4 ± 444 vs. non-DM: 773.1 ± 348.2; p = 0.04), but similar p-tau (p = 0.72) and Aß1-42  levels (p = 0.83). Furthermore, multivariable regression analyses showed a significant association between DM and t-tau CSF levels, adjusting for age and sex, in APOE E4+ carriers (coefficient 222.83, 95% confidence interval 47.49-398.1; p = 0.01), but not in APOE E4- (p = 0.53). CONCLUSIONS: The present study shows a clear dependency of CSF t-tau levels on DM for APOE E4+ AD patients, suggesting important differences between APOE E4-related and non-related disease, with key implications for AD pathophysiology and treatment.

Brain energy metabolism and neurodegeneration: hints from CSF lactate levels in dementias.

Mitochondrial dysfunction is pivotal in the development of neurodegenerative dementias, causing cellular death alongside disease-specific pathogenic cascades. Holding cerebrospinal fluid (CSF) lactates as an indirect measure of brain metabolic activity, we first compared CSF lactate levels from patients with Alzheimer's disease (AD)-stratified according to the ATN system and epsilon genotype-frontotemporal dementia (FTD) and dementia with Lewy body (DLB) to findings from healthy controls. With respect to controls, we detected lower CSF lactates in patients with AD and FTD but comparable levels in patients with DLB. Second, a correlation analysis between CSF lactates and biomarkers of neurodegeneration identified an inverse correlation between lactates and levels of t-tau and p-tau only in the Alzheimer's continuum. The reduction of CSF lactate correlates to the advent of tauopathy and cellular death in AD, implying that Aß pathology alone is not sufficient to induce neuronal metabolic impairment. The metabolic impairment in FTD patients has a similar explanation, as it is likely due to fast neuronal degeneration in the disease. The absence of CSF lactate reduction in patients with DLB may be related to the prevalent subcortical localization of the pathology.

Efficacy and safety of lacosamide in the treatment of status epilepticus in a patient with comorbidities.

Efficacy, safety and tolerability of lacosamide in the treatment of status epilepticus are well described. However, other evidence of its pharmacologic profile in elderly patients with other comorbidities seems warranted. We describe the case of an 80 year-old woman with an history of arterial hypertension, ischemic cardiomyopathy, COPD, CKD, previous laryngeal cancer, a stoma positioning for diverticular disease and previous surgery for a left frontal meningioma. Since then, the patient developed focal epilepsy and she was on levetiracetam and valproic acid therapy. The patient was admitted to our department for a focal status epilepticus characterized by non-fluent aphasia and right facio-brachial clonic movements. She also presented with aspiration pneumonia and started intravenous antibiotic treatment. After failure of a first-line antiepileptic drug, lacosamide intravenous treatment was started, with complete reversal of the clinical picture. EEG then showed focal slow waves mixed to interictal epileptiform discharges over the left fronto-temporal regions. The patient was then discharged home with an oral lacosamide treatment and at 3 months she was seizure-free. Our case report confirms the efficacy of lacosamide in status epilepticus, highlighting its safety and tolerability in an elderly and fragile patient with multiple comorbidities and drug therapy.

Haemodynamic impairment along the Alzheimer's disease continuum.

BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is considered a clinical and biological continuum identified via cerebrospinal fluid (CSF) or imaging biomarkers. Chronic hypoperfusion is held as one of the main features of Alzheimer's disease, as part of the processes causing neuronal degeneration. The mechanism responsible for such condition is still debated, although recently a direct connection with amyloid peptides has been shown. Here the aim was to investigate whether measures of hypoperfusion change along the AD continuum. METHODS: Seventy patients with mild AD were recruited and stratified according to their CSF biomarker profile-as indicated by the National Institute on Aging and Alzheimer's Association research framework-into patients with either isolated amyloid pathology (A+T-) or full-blown AD (A+T+), and further layered according to apolipoprotein E genotype. After evaluation of vascular risk factors, a transcranial Doppler was performed on each patient, to evaluate mean flow velocity and pulsatility index in the middle cerebral artery, and to calculate the breath-holding index. Patients were compared to a cohort of 17 healthy controls. RESULTS: The breath-holding index was reduced in the AD continuum and was inversely correlated to CSF amyloid ß42 levels. Such correlation was stronger in the A+T+ than in the A+T- group, and unexpectedly reached statistical significance only in the E3 and not in the E4 genotype carriers. CONCLUSIONS: These results suggest a tight and effective relationship between amyloid ß42, vascular hypoperfusion, cerebrovascular reactivity and epsilon genotype.

Mechanical Thrombectomy for Acute Intracranial Carotid Occlusion with Patent Intracranial Arteries : The Italian Registry of Endovascular Treatment in Acute Stroke.

PURPOSE: Intracranial carotid artery occlusion represents an underinvestigated cause of acute ischemic stroke as well as an indication for mechanical thrombectomy. We investigated baseline and procedural characteristics, outcomes and predictors of outcome in patients with acute ischemic stroke secondary to intracranial carotid artery occlusion. METHODS: A retrospective analysis of the Italian Registry of Endovascular Treatment in Acute Stroke was performed. Patients with intracranial carotid artery occlusion (infraclinoid and supraclinoid) with or without cervical artery occlusion but with patent intracranial arteries were included. The 3­month functional independence, mortality, successful reperfusion and symptomatic intracranial hemorrhage were evaluated. RESULTS: Intracranial carotid artery occlusion with patent intracranial arteries was diagnosed in 387 out of 4940 (7.8%) patients. The median age was 74 years and median baseline National Institute of Health Stroke Scale (NIHSS) was 18. Functional independence was achieved in 130 (34%) patients, successful reperfusion in 289 (75%) and symptomatic intracranial hemorrhage in 33 (9%), whereas mortality occurred in 111 (29%) patients. In univariate analysis functional independence was associated with lower age, lower NIHSS at presentation, higher rate of successful reperfusion and lower rate of symptomatic intracranial hemorrhage. Multivariable regression analysis found age (odds ratio, OR:1.03; P = 0.006), NIHSS at presentation (OR: 1.07; P < 0.001), diabetes (OR: 2.60; P = 0.002), successful reperfusion (OR:0.20; P < 0.001) and symptomatic intracranial hemorrhage (OR: 4.17; P < 0.001) as the best independent predictors of outcome. CONCLUSION: Our study showed a not negligible rate of intracranial carotid artery occlusion with patent intracranial arteries, presenting mostly as severe stroke, with an acceptable rate of 3­month functional independence. Age, NIHSS at presentation and successful reperfusion were the best independent predictors of outcome.

Clinical worsening despite intravenous thrombolysis in acute ischemic stroke secondary to carotid plaque rupture.

First-line therapy of acute ischemic stroke is intravenous thrombolysis (IVT) irrespective of etiology. We report on a patient with acute ischemic stroke secondary to carotid plaque rupture who experienced plaque thrombosis and marked clinical worsening despite IVT. While the latter is the gold standard therapy optimal platelets inhibition should be guaranteed to allow a safe as possible carotid intervention. Hereby we discuss all available strategies to be considered in order to better individualized treatment decision-making.

Selection of anterior circulation acute stroke patients for mechanical thrombectomy.

BACKGROUND: The use of mechanical thrombectomy (MT) for acute ischemic stroke (AIS) patients has increased with a parallel burden in procedural costs. We tested whether a new prognostic score could identify patients who are unlikely to benefit from MT. METHODS: Patients from our endovascular stroke registry were assessed for imaging and clinical outcome measures and randomly divided into two subsets for derivation and validation. We created a new prognostic score based on clinical and radiological prognostic factors of poor outcome (mRS score ≥ 3) from the derivation cohort. Receiver operating characteristics curve analysis was used to assess the discrimination ability of the score. The score was then validated and compared to the MR PREDICTS score. RESULTS: The derivation/validation included 270/116 patients, respectively. After multivariate logistic regression analysis, pre stroke mRS, age, admission glycaemia, admission NIHSS, collateral flow, Clot Burden Score, Alberta Stroke Program Early CT score were used to create a new prognostic scoring system called Tor Vergata Stroke Score (TVSS). TVSS revealed a good prognostic accuracy with an AUC of 0.825 [95% CI 0.77-0.88] in the derivation cohort and an AUC of 0.820 [95% CI 0.74-0.90] in the validation cohort. When compared to the MR PREDICTS in the validation cohort, TVSS demonstrated higher prediction ability which was, however, not statistically significant (0.80 vs 0.78; P = 0.26). CONCLUSIONS: TVSS is a reliable tool for selection of AIS candidates for MT and optimization of transfer to comprehensive stroke centers.

Safety and Efficacy of Reperfusion Therapies for Acute Ischemic Stroke Patients with Active Malignancy.

BACKGROUND AND PURPOSE: Epidemiological correlations between active malignancy (AM) and acute ischemic stroke (AIS) are well-established. However, the effect of reperfusion strategies, particularly mechanical thrombectomy (MT), has been barely investigated in patients with AIS and AM. We aim to evaluate safety and efficacy of reperfusion strategies in such patients. MATERIALS AND METHODS: We performed a case-control analysis comparing patients with AM and AIS (AM group) to a group of cancer-free patients with AIS (control group). All enrolled patients underwent reperfusion therapies (i.e. intravenous thrombolysis, MT, intravenous thrombolysis plus MT). Main outcomes were 3-month functional independence, successful reperfusion, 3-month mortality, symptomatic intracranial hemorrhage. RESULTS: Total 24 patients with AM and AIS (mean age: 69 ± 10.1) were individually matched to 24 control patients (mean age: 70.7 ± 9.3). In both groups 50% were treated with MT, 46% with intravenous thrombolysis and 4% with intravenous thrombolysis plus MT. No difference were found in successful reperfusion, 3-month functional independence, symptomatic intracranial hemorrhage, and mortality. However an overall mortality of 33% in the AM group was reported. CONCLUSIONS: Reperfusion strategies for AIS patients with AM seem to be safe and effective. However an individualized approach to understand cancer stage and life-expectation is warranted.