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.

Internal carotid artery patency after mechanical thrombectomy for stroke due to occlusive dissection: Impact on outcome.

Introduction: Internal carotid artery dissection (ICAD) is a rare cause of acute ischemic stroke with large vessel occlusion (AIS-LVO). We aimed investigating the impact on outcome of internal carotid artery (ICA) patency after mechanical thrombectomy (MT) for AIS-LVO due to occlusive ICAD. Patients and methods: We included consecutive patients with AIS-LVO due to occlusive ICAD treated with MT from January 2015 to December 2020 in three European stroke centers. We excluded patients with unsuccessful intracranial reperfusion after MT (modified Thrombolysis in Cerebral Infarction (mTICI) score < 2b). We compared 3-month favorable clinical outcome rate, defined as a modified Rankin scale (mRS) score ⩽2, according to ICA status (patency vs occlusion) at the end of MT and at 24-h follow-up imaging, using univariate and multivariable models. Results: Among 70 included patients, ICA was patent in 54/70 (77%) at the end of MT, and in 36/66 (54.5%) patients with 24-h follow-up imaging. Among patients with ICA patency at the end of MT, 32% presented ICA occlusion at 24-h control imaging. Favorable 3-month outcome occurred in 41/54 (76%) patients with ICA patency post-MT and in 9/16 (56%) patients with occluded ICA post-MT (p = 0.21). Rates of favorable outcome were significantly higher in patients with 24-h ICA patency compared to patients with 24-h ICA occlusion (32/36 [89%] vs 15/30 [50%]), with an adjusted odds ratio of 4.67 (95% CI: 1.26-17.25). Discussion and conclusion: Obtaining sustained (24-h) ICA patency after MT could be a therapeutic target for improving functional outcome in patients with AIS-LVO due to ICAD.

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.

Endovascular treatment of patients with acute ischemic stroke and tandem occlusion due to internal carotid artery dissection: A multicenter experience.

BACKGROUND: The optimal management of patients with acute ischemic stroke (AIS) due to tandem occlusion (TO) and underlying carotid dissection (CD) remains unclear. OBJECTIVE: We present our multicenter-experience of endovascular treatment (EVT) approach used and outcomes for AIS patients with CD-related TO (CD-TO). METHODS: Consecutive AIS patients underwent EVT for CD-TO at five Italian Neuro-interventional Tertiary Stroke Centers were retrospectively identified. TO from atherosclerosis and other causes of, were excluded from the final analysis. Primary outcome was successful (mTICI 2b-3) and complete reperfusion (mTICI 3); secondary outcome was patients' 3-months functional independence (mRS≤2). RESULTS: Among 214 AIS patients with TO, 45 presented CD-TO. Median age was 54 years (range 29-86), 82.2% were male. Age <65 years (p < 0.0001), lower baseline NIHSS score (p = 0.0002), and complete circle of Willis (p = 0.0422) were associated with mRS ≤ 2 at the multivariate analysis. Comparisons between antegrade and retrograde approaches resulted in differences for baseline NIHSS scores (p = 0.001) and number of EVT attempts per-procedure (p = 0.001). No differences in terms of recanalization rates were observed between antegrade and retrograde EVT approaches (p = 0.811) but higher rates of mTICI3 revascularization was observed with the retrograde compared to the antegrade approach (78.6% vs 73.3%), anyway not statistically significant. CD management technique (angioplasty vs aspiration vs emergent stenting) did not correlate with 3-months mRS≤2. CONCLUSION: AIS patients with CD-TO were mostly treated with the retrograde approach with lower number of attempts per-procedure but it offered similar recanalization rates compared with the antegrade approach. Emergent carotid artery stenting (CAS) proved to be safe for CD management but it does not influence 3-months patients' clinical outcomes.

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.

Early-onset delirium after spontaneous intracerebral hemorrhage.

OBJECTIVE: This study aimed at identifying the incidence, predictors, and impact on long-term mortality and dementia of early-onset delirium in a cohort of patients with spontaneous intracerebral hemorrhage. METHODS: We prospectively recruited consecutive patients in the Prognosis of InTra-Cerebral Hemorrhage (PITCH) cohort and analyzed incidence rate of early-onset delirium (i.e. during the first seven days after intracerebral hemorrhage onset) with a competing risk model. We used a multivariable Fine-Gray model to identify baseline predictors, a Cox regression model to study its impact on the long-term mortality risk, and a Fine-Gray model adjusted for pre-specified confounders to analyze its impact on new-onset dementia. RESULTS: The study population consisted of 248 patients (mean age 70 years, 54% males). Early-onset delirium incidence rate was 29.8% (95% confidence interval (CI) 24.3-35.6). Multivariate analysis showed that pre-existing dementia (subhazard ratio (SHR) 2.08, 95%CI 1.32-3.32, p = 0.002), heavy alcohol intake (SHR 1.79, 95%CI 1.13-2.82, p = 0.013), and intracerebral hemorrhage lobar location (SHR 1.56, 95%CI 1.01-2.42, p = 0.049) independently predicted early-onset delirium. Median follow-up was 9.5 years. Early-onset delirium was associated with higher mortality rates during the first five years of follow-up (HR 1.52, 95%CI 1.00-2.31, p = 0.049), but did not predict new-onset dementia (SHR 1.31, 95%CI 0.60-2.87). CONCLUSION: Early-onset delirium is a frequent complication after intracerebral hemorrhage; it is associated with markers of pre-existing brain vulnerability and with higher mortality risk, but not with higher dementia rates during long-term follow-up.

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.

Design of a multiplex ligation-dependent probe amplification assay for SLC20A2: identification of two novel deletions in primary familial brain calcification.

Primary familial brain calcification (PFBC) is a rare disease characterized by brain calcifications that mainly affect the basal ganglia, thalamus, and cerebellum. Among the four autosomal-dominant genes known to be associated with the disease, SLC20A2 pathogenic variants are the most common, accounting for up to 40% of PFBC dominant cases; variants include both point mutations, small insertions/deletions and intragenic deletions. Over the last 7 years, we have collected a group of 50 clinically diagnosed PFBC patients, who were screened for single nucleotide changes and small insertions/deletions in SLC20A2 by Sanger sequencing. We found seven pathogenic/likely pathogenic variants: four were previously described by our group, and three are reported here (c.303delG, c.21delG, and c.1795-1G>A). We developed and validated a synthetic Multiplex Ligation-dependent Probe Amplification (MLPA) assay for SLC20A2 deletions, covering all ten coding exons and the 5' UTR (SLC20A2-MLPA). Using this method, we screened a group of 43 PFBC-patients negative for point mutations and small insertions/deletions, and identified two novel intragenic deletions encompassing exon 6 NC_000008.10:g.(42297172_42302163)_(423022281_42317413)del, and exons 7-11 including the 3'UTR NC_000008.10:g.(?_42275320)_(42297172_42302163)del. Overall, SLC20A2 deletions may be highly underestimated PFBC cases, and we suggest MLPA should be included in the routine molecular test for PFBC diagnosis.

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.