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.

Myosteatosis as an independent predictor of short-term mortality in successfully reperfused acute ischemic stroke.

BACKGROUND AND PURPOSE: Poor clinical outcomes are still common in successfully reperfused acute ischemic stroke patients. The aim of our study was to assess the impact of sarcopenia and myosteatosis on neurological outcomes and mortality in successfully reperfused acute ischemic stroke patients. MATERIALS AND METHODS: We included in our retrospective observational study 166 consecutive patients who underwent technically successful mechanical thrombectomy for anterior circulation acute ischemic stroke between Jan 2016 and Dec 2019. ASPECTS and collateral score were assessed on pre-operative CT/CTA. Masseter muscles area and attenuation were measured on CTA images. Clinical and radiological variables were tested in multivariate logistic models to predict the probability of death and, among survivors, of incurring poor outcome. RESULTS: At admission, mean NIHSS was 19 (SD = 6.5), mean body mass index 25.5 (SD = 4.4) kg/m2, and mean ASPECTS 8.0 (SD = 1.9). Of all, 48.2% patients showed good collaterals, 38.5% intermediate collaterals, and 13.3% poor collaterals. Overall, 90 days mRS was ≤2 in 48.2% of the patients, 3-5 in 30.7%, and 6 in 21.1%. At multivariate logistic regression, age (OR = 1.08, p = 0.036), ASPECTS (OR = 0.59, p = 0.013), and masseter muscles attenuation (OR = 0.93, p = 0.010) were independent predictors of mortality, whereas sex (OR = 7.15, p = 0.043), age (OR = 1.05, p = 0.042), body mass index (OR = 1.35, p = 0.013), NIHSS (OR = 1.12, p = 0.012), and ASPECTS (OR = 0.64, p = 0.024) were independent predictors of poor neurological outcome (mRS 3-5). CONCLUSION: Beyond other well-known variables, low masseter attenuation, indicating myosteatosis, represents an independent negative prognostic factor for 90 days mortality in patients successfully reperfused after anterior circulation stroke.

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.

Sex differences in outcome after thrombectomy for acute ischemic stroke. A propensity score-matched study.

Background and purpose: We sought to investigate whether there are gender differences in clinical outcome after stroke due to large vessel occlusion (LVO) after mechanical thrombectomy (EVT) in a large population of real-world patients. Methods: From the Italian Registry of Endovascular Thrombectomy, we extracted clinical and outcome data of patients treated for stroke due to large vessel occlusion. We compared clinical and safety outcomes in men and women who underwent EVT alone or in combination with intravenous thrombolysis (IVT) in the total population and in a Propensity Score matched set. Results: Among 3422 patients included in the study, 1801 (52.6%) were women. Despite older age at onset (mean 72.4 vs 68.7; p < 0.001), and higher rate of atrial fibrillation (41.7% vs 28.6%; p < 0.001), women had higher probability of 3-month functional independence (adjusted odds ratio-adjOR 1.19; 95% CI 1.02-1.38), of complete recanalization (adjOR 1.25; 95% CI 1.09-1.44) and lower probability of death (adjOR 0.75; 95% CI 0.62-0.90). After propensity-score matching, a well-balanced cohort comprising 1150 men and 1150 women was analyzed, confirming the same results regarding functional outcome (3-month functional independence: OR 1.25; 95% CI 1.04-1.51), and complete recanalization (OR 1.29; 95% CI 1.09-1.53). Conclusions: Subject to the limitations of a non-randomized comparison, women with stroke due to LVO treated with mechanical thrombectomy had a better chance to achieve complete recanalization, and 3-month functional independence than men. The results could be driven by women who underwent combined treatment.

Stroke management during the coronavirus disease 2019 (COVID-19) pandemic: experience from three regions of the north east of Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige).

BACKGROUND: Efficiency of care chain response and hospital reactivity were and are challenged for stroke acute care management during the pandemic period of coronavirus disease 2019 (COVID-19) in North-Eastern Italy (Veneto, Friuli-Venezia-Giulia, Trentino-Alto-Adige), counting 7,193,880 inhabitants (ISTAT), with consequences in acute treatment for patients with ischemic stroke. METHODS: We conducted a retrospective data collection of patients admitted to stroke units eventually treated with thrombolysis and thrombectomy, ranging from January to May 2020 from the beginning to the end of the main first pandemic period of COVID-19 in Italy. The primary endpoint was the number of patients arriving to these stroke units, and secondary endpoints were the number of thrombolysis and/or thrombectomy. Chi-square analysis was used on all patients; furthermore, patients were divided into two cohorts (pre-lockdown and lockdown periods) and the Kruskal-Wallis test was used to test differences on admission and reperfusive therapies. RESULTS: In total, 2536 patients were included in 22 centers. There was a significant decrease of admissions in April compared to January. Furthermore, we observed a significant decrease of thrombectomy during the lockdown period, while thrombolysis rate was unaffected in the same interval across all centers. CONCLUSIONS: Our study confirmed a decrease in admission rate of stroke patients in a large area of northern Italy during the lockdown period, especially during the first dramatic phase. Overall, there was no decrease in thrombolysis rate, confirming an effect of emergency care system for stroke patients. Instead, the significant decrease in thrombectomy rate during lockdown addresses some considerations of local and regional stroke networks during COVID-19 pandemic evolution.

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.

Complications of mechanical thrombectomy for acute ischemic stroke: Incidence, risk factors, and clinical relevance in the Italian Registry of Endovascular Treatment in acute stroke.

BACKGROUND: There are limited data concerning procedure-related complications of endovascular thrombectomy for large vessel occlusion strokes. AIMS: We evaluated the cumulative incidence, the clinical relevance in terms of increased disability and mortality, and risk factors for complications. METHODS: From January 2011 to December 2017, 4799 patients were enrolled by 36 centers in the Italian Registry of Endovascular Stroke Treatment. Data on demographic and procedural characteristics, complications, and clinical outcome at three months were prospectively collected. RESULTS: The complications cumulative incidence was 201 per 1000 patients undergoing endovascular thrombectomy. Ongoing antiplatelet therapy (p < 0.01; OR 1.82, 95% CI: 1.21-2.73) and large vessel occlusion site (carotid-T, p < 0.03; OR 3.05, 95% CI: 1.13-8.19; M2-segment-MCA, p < 0.01; OR 4.54, 95% CI: 1.66-12.44) were associated with a higher risk of subarachnoid hemorrhage/arterial perforation. Thrombectomy alone (p < 0.01; OR 0.50, 95% CI: 0.31-0.83) and younger age (p < 0.04; OR 0.98, 95% CI: 0.97-0.99) revealed a lower risk of developing dissection. M2-segment-MCA occlusion (p < 0.01; OR 0.35, 95% CI: 0.19-0.64) and hypertension (p < 0.04; OR 0.77, 95% CI: 0.6-0.98) were less related to clot embolization. Higher NIHSS at onset (p < 0.01; OR 1.04, 95% CI: 1.02-1.06), longer groin-to-reperfusion time (p < 0.01; OR 1.05, 95% CI: 1.02-1.07), diabetes (p < 0.01; OR 1.67, 95% CI: 1.25-2.23), and LVO site (carotid-T, p < 0.01; OR 1.96, 95% CI: 1.26-3.05; M2-segment-MCA, p < 0.02; OR 1.62, 95% CI: 1.08-2.42) were associated with a higher risk of developing symptomatic intracerebral hemorrhage compared to no/asymptomatic intracerebral hemorrhage. The subgroup of patients treated with thrombectomy alone presented a lower risk of symptomatic intracerebral hemorrhage (p < 0.01; OR 0.70; 95% CI: 0.55-0.90). Subarachnoid hemorrhage/arterial perforation and symptomatic intracerebral hemorrhage after endovascular thrombectomy worsen both functional independence and mortality at three-month follow-up (p < 0.01). Distal embolization is associated with neurological deterioration (p < 0.01), while arterial dissection did not affect clinical outcome at follow-up. CONCLUSIONS: Complications globally considered are not uncommon and may result in poor clinical outcome. Early recognition of risk factors might help to prevent complications and manage them appropriately in order to maximize endovascular thrombectomy benefits.

IER-START nomogram for prediction of three-month unfavorable outcome after thrombectomy for stroke.

BACKGROUND: The applicability of the current models for predicting functional outcome after thrombectomy in strokes with large vessel occlusion (LVO) is affected by a moderate predictive performance. AIMS: We aimed to develop and validate a nomogram with pre- and post-treatment factors for prediction of the probability of unfavorable outcome in patients with anterior and posterior LVO who received bridging therapy or direct thrombectomy <6 h of stroke onset. METHODS: We conducted a cohort study on patients data collected prospectively in the Italian Endovascular Registry (IER). Unfavorable outcome was defined as three-month modified Rankin Scale (mRS) score 3-6. Six predictors, including NIH Stroke Scale (NIHSS) score, age, pre-stroke mRS score, bridging therapy or direct thrombectomy, grade of recanalization according to the thrombolysis in cerebral ischemia (TICI) grading system, and onset-to-end procedure time were identified a priori by three stroke experts. To generate the IER-START, the pre-established predictors were entered into a logistic regression model. The discriminative performance of the model was assessed by using the area under the receiver operating characteristic curve (AUC-ROC). RESULTS: A total of 1802 patients with complete data for generating the IER-START was randomly dichotomized into training (n = 1219) and test (n = 583) sets. The AUC-ROC of IER-START was 0.838 (95% confidence interval [CI]): 0.816-0.869) in the training set, and 0.820 (95% CI: 0.786-0.854) in the test set. CONCLUSIONS: The IER-START nomogram is the first prognostic model developed and validated in the largest population of stroke patients currently candidates to thrombectomy which reliably calculates the probability of three-month unfavorable outcome.

IER-SICH Nomogram to Predict Symptomatic Intracerebral Hemorrhage After Thrombectomy for Stroke.

Background and Purpose- As a reliable scoring system to detect the risk of symptomatic intracerebral hemorrhage after thrombectomy for ischemic stroke is not yet available, we developed a nomogram for predicting symptomatic intracerebral hemorrhage in patients with large vessel occlusion in the anterior circulation who received bridging of thrombectomy with intravenous thrombolysis (training set), and to validate the model by using a cohort of patients treated with direct thrombectomy (test set). Methods- We conducted a cohort study on prospectively collected data from 3714 patients enrolled in the IER (Italian Registry of Endovascular Stroke Treatment in Acute Stroke). Symptomatic intracerebral hemorrhage was defined as any type of intracerebral hemorrhage with increase of ≥4 National Institutes of Health Stroke Scale score points from baseline ≤24 hours or death. Based on multivariate logistic models, the nomogram was generated. We assessed the discriminative performance by using the area under the receiver operating characteristic curve. Results- National Institutes of Health Stroke Scale score, onset-to-end procedure time, age, unsuccessful recanalization, and Careggi collateral score composed the IER-SICH nomogram. After removing Careggi collateral score from the first model, a second model including Alberta Stroke Program Early CT Score was developed. The area under the receiver operating characteristic curve of the IER-SICH nomogram was 0.778 in the training set (n=492) and 0.709 in the test set (n=399). The area under the receiver operating characteristic curve of the second model was 0.733 in the training set (n=988) and 0.685 in the test set (n=779). Conclusions- The IER-SICH nomogram is the first model developed and validated for predicting symptomatic intracerebral hemorrhage after thrombectomy. It may provide indications on early identification of patients for more or less postprocedural intensive management.

Low risk of seizures with slow flumazenil infusion and routine anticonvulsant prophylaxis for high-dose benzodiazepine dependence.

High-dose benzodiazepine (BZD) dependence represents an emerging and under-reported addiction phenomenon and is associated with reduced quality of life. To date there are no guidelines for the treatment of high-dose BZD withdrawal. Low-dose slow flumazenil infusion was reported to be effective for high-dose BZD detoxification, but there is concern about the risk of convulsions during this treatment. We evaluated the occurrence of seizures in 450 consecutive high-dose BZD dependence patients admitted to our unit from April 2012 to April 2016 for detoxification with low-dose slow subcutaneous infusion of flumazenil associated with routine anticonvulsant prophylaxis. In our sample, 22 patients (4.9%) reported history of convulsions when previously attempting BZD withdrawal. Only four patients (0.9%) had seizures during ( n = 2) or immediately after ( n = 2) flumazenil infusion. The two patients with seizures during flumazenil infusion were poly-drug misusers. The most common antiepileptic drugs (AEDs) used for anticonvulsant prophylaxis were either valproate 1000 mg or levetiracetam 1000 mg. Our data indicate that, when routinely associated with AEDs prophylaxis, low-dose slow subcutaneous flumazenil infusion represents a safe procedure, with low risk of seizure occurrence.

A multimodal imaging approach to the evaluation of post-traumatic epilepsy.

OBJECT: Electroencephalography-functional magnetic resonance imaging (EEG-fMRI) coregistration and high-density EEG (hdEEG) can be combined to map noninvasively abnormal brain activation elicited by epileptic processes. By combining noninvasive imaging techniques in a multimodal approach, we sought to investigate pathophysiological mechanisms underlying epileptic activity in seven patients with severe traumatic brain injury. MATERIALS AND METHODS: Standard EEG and fMRI data were acquired during a single scanning session. The EEG-fMRI data were analyzed using the general linear model and independent component analysis. Source localization of interictal epileptiform discharges (IEDs) was performed using 256-channel hdEEG. Blood oxygenation level dependent (BOLD) localizations were then compared to EEG source reconstruction. RESULTS: On hdEEG, focal source localization was detected in all seven patients; in six out of seven it was concordant with the expected epileptic activity as defined by EEG data and clinical evaluation; and in four out of seven in whom IEDs were recorded, BOLD signal changes were observed. These activities were partially concordant with the source localization. CONCLUSION: Multimodal integration of EEG-fMRI and hdEEG combining two different methods to localize the same epileptic foci appears to be a promising tool to noninvasively map abnormal brain activation in patients with post-traumatic brain injury.