Botulinum neurotoxin as early treatment in acute-onset lesional hemiballism.

BACKGROUND: Hemiballism (HB) and hemichorea (HC) are the most frequent secondary movement disorders, usually caused by cerebrovascular diseases. In only a minority of cases, these involuntary movements are not self-limited, and they may severely compromise patients' quality of life, so that symptomatic treatments are required. Typical and atypical neuroleptics as well as tetrabenazine are considered therapies of choice. However, anecdotal reports of antiseizures medications and botulinum neurotoxin injection effectiveness have been described. METHODS: We described a case of severely disabling acute-onset lesional HB/HC, where high dosage of first- and second-line therapies was contraindicated due to patient's comorbidities. RESULTS: After botulin neurotoxin (BoNT) injections in his left upper limb muscles (biceps brachii, triceps brachii, teres major, and deltoid), the patient experienced gradual reduction of hyperkinetic movements. The gradual discontinuation of topiramate (TPM) did not worsen the clinical picture. DISCUSSION: The reduction of hyperkinetic movements led to rhabdomyolysis resolution as well as cutaneous injuries healing with renal function improvement, so that the patient was able to be eligible for rehabilitation, which was prevented by HB/HC itself. The clinical improvement was consistent with BoNT pharmacokinetic. The administration of BoNT early after the onset of lesional HB/HC remarkably modified the clinical management and drove toward comorbidities resolution and rehabilitation. CONCLUSION: The present case highlights the effectiveness of unconventional therapeutic options in disabling acute onset lesional HB/HC when first-line therapies are contraindicated. Particularly, this report may encourage BoNT application in the early stage of movement disorder emergencies.

Prevalence of Fabry disease and GLA variants in young patients with acute stroke: The challenge to widen the screening. The Fabry-Stroke Italian Registry.

BACKGROUND: Fabry disease (FD) is a treatable X-linked lysosomal storage disorder caused by GLA gene variants leading to alpha-galactosidase A deficiency. FD is a rare cause of stroke, and it is still controversial whether in stroke patients FD should be searched from the beginning or at the end of the diagnostic workup (in cryptogenic strokes). METHODS: Fabry-Stroke Italian Registry is a prospective, multicentric screening involving 33 stroke units. FD was sought by measuring α-galactosidase A activity (males) and by genetic tests (males with reduced enzyme activity and females) in patients aged 18-60 years hospitalized for TIA, ischemic stroke, or intracerebral hemorrhage. We diagnosed FD in patients with 1) already known pathogenic GLA variants; 2) novel GLA variants if additional clinical, laboratory, or family-derived criteria were present. RESULTS: Out of 1906 patients, we found a GLA variant in 15 (0.79%; 95%CI 0.44-1.29) with a certain FD diagnosis in 3 (0.16%; 95%CI 0.03-0.46) patients, none of whom had hemorrhage. We identified 1 novel pathogenic GLA variant. Ischemic stroke etiologies in carriers of GLA variants were: cardioaortic embolism (33%), small artery occlusion (27%), other causes (20%), and undetermined (20%). Mild severity, recurrence, previous TIA, acroparesthesias, hearing loss, and small artery occlusion were predictors of GLA variant. CONCLUSION: In this large multicenter cohort the frequency of FD and GLA variants was consistent with previous reports. Limiting the screening for GLA variants to patients with cryptogenic stroke may miss up to 80% of diagnoses. Some easily recognizable clinical features could help select patients for FD screening.

IV thrombolysis plus thrombectomy versus IV thrombolysis alone for minor stroke with anterior circulation large vessel occlusion from the IRETAS and Italian SITS-ISTR cohorts.

INTRODUCTION: The aim of this study was to compare the outcomes of patients treated with intravenous thrombolysis (IVT) <4.5 h after symptom onset plus mechanical thrombectomy (MT) <6 h with those treated with IVT alone <4.5 h for minor stroke (NIHSS ≤5) with large vessel occlusion (LVO) in the anterior circulation. PATIENTS AND METHODS: Patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) and in the Italian centers included in the SITS-ISTR were analyzed. RESULTS: Among the patients with complete data on 24-h ICH type, 236 received IVT plus MT and 382 received IVT alone. IVT plus MT was significantly associated with unfavorable shift on 24-h ICH types (from no ICH to PH-2) (OR, 2.130; 95% CI, 1.173-3.868; p=0.013) and higher rate of PH (OR, 4.363; 95% CI, 1.579-12.055; p=0.005), sICH per ECASS II definition (OR, 5.527; 95% CI, 1.378-22.167; p=0.016), and sICH per NINDS definition (OR, 3.805; 95% CI, 1.310-11.046; p=0.014). Among the patients with complete data on 3-month mRS score, 226 received IVT plus MT and 262 received IVT alone. No significant difference was reported between IVT plus MT and IVT alone on mRS score 0-1 (72.1% versus 69.1%), mRS score 0-2 (79.6% versus 79%), and death (6.2% versus 6.1%). CONCLUSIONS: Compared with IVT alone, IVT plus MT was associated with unfavorable shift on 24-h ICH types and higher rate of 24-h PH and sICH in patients with minor stroke and LVO in the anterior circulation. However, no difference was reported between the groups on 3-month functional outcome measures.

Intracranial Stenosis Treated with Stenting in Patients with Suspected Cerebral Vasculitis: Two Case Reports.

Central nervous system vasculitis (CNSV) is an uncommon and poorly understood form of vasculitis. Early recognition is important because medical treatment might improve the outcome. However, randomized clinical trials on CNSV treatment do not exist. Endovascular treatment has been reported in few cases, but no data exist for intracranial stenting. We report 2 cases of patients with suspected CNSV and recurrent clinical episodes, treated with intracranial stenting. A 48-year-old man had relapsing episodes of right hemiparesis. Neuroradiological exams showed severe left carotid terminus stenosis. Despite immunosuppressive therapy, neuroradiological follow-up exams showed a worsening of the aforementioned stenosis with many transient episodes of weakness in the right limbs and aphasia. A 64-year-old woman had a sudden onset of dysarthria and transient aphasia. Neuroradiological exams showed a severe arterial stenosis involving the origin of left anterior cerebral artery and middle cerebral artery (MCA). Despite dual antiplatelet therapy, she presented an acute onset of severe aphasia, due to an occlusion of the left carotid terminus and proximal MCA. In both cases, endovascular procedure and intracranial stenting was performed, with marked improvement of cerebral blood flow. No more clinical episodes were reported. Intracranial stenting may be a valid therapeutic option in selected patients with CNSV and involvement of medium or large size vessels with clinical worsening despite best medical treatment.

Stroke with large vessel occlusion in the posterior circulation: IV thrombolysis plus thrombectomy versus IV thrombolysis alone.

Efficacy and safety of mechanical thrombectomy (MT) for stroke with posterior circulation large vessel occlusion (LVO) is still under debate. We aimed to compare the outcomes of stroke patients with posterior circulation LVO treated with intravenous thrombolysis (IVT) (< 4.5 h after symptom onset) plus MT < 6 h after symptom onset with those treated with IVT alone (< 4.5 h after symptom onset). Patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) and in the Italian centers included in the SITS-ISTR were analysed. We identified 409 IRETAS patients treated with IVT plus MT and 384 SITS-ISTR patients treated with IVT alone. IVT plus MT was significantly associated with higher rate of sICH (ECASS II) compared with IVT alone (3.1 vs 1.9%; OR 3.984, 95% CI 1.014-15.815), while the two treatments did not differ significantly in 3-month mRS score ≤ 3 (64.3 vs 74.1%; OR 0.829, 95% CI 0.524-1.311). In 389 patients with isolated basilar artery (BA) occlusion, IVT plus MT was significantly associated with higher rate of any ICH compared with IVT alone (9.4 vs 7.4%; OR 4.131, 95% CI 1.215-14.040), while two treatments did not differ significantly in 3-month mRS score ≤ 3 and sICH per ECASS II definition. IVT plus MT was significantly associated with higher rate mRS score ≤ 2 (69.1 vs 52.1%; OR 2.692, 95% CI 1.064-6.811) and lower rate of death (13.8 vs 27.1%; OR 0.299, 95% CI 0.095-0.942) in patients with distal-segment BA occlusion, while two treatments did not differ significantly in 3-month mRS score ≤ 3 and sICH per ECASS II definition. IVT plus MT was significantly associated with lower rate of mRS score ≤ 3 (37.1 vs 53.3%; OR 0.137, 0.009-0.987), mRS score ≤ 1 (22.9 vs 53.3%; OR 0.066, 95% CI 0.006-0.764), mRS score ≤ 2 (34.3 vs 53.3%; OR 0.102, 95% CI 0.011-0.935), and higher rate of death (51.4 vs 40%; OR 16.244, 1.395-89.209) in patients with proximal-segment BA occlusion. Compared with IVT alone, IVT plus MT was significantly associated with higher rate of sICH per ECASS II definition in patients with stroke and posterior circulation LVO, while two treatment groups did not differ significantly in 3-month mRS score ≤ 3. IVT plus MT was associated with lower rate of mRS score ≤ 3 compared with IVT alone in patients with proximal-segment BA occlusion, whereas no significant difference was found between the two treatments in primary endpoints in patients isolated BA occlusion and in the other subgroups based on site occlusion.

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.

Predictors for clinical and functional outcomes in stroke patients with first-pass complete recanalization after thrombectomy.

BACKGROUND AND PURPOSE: The aim was to identify baseline clinical and radiological/procedural predictors and 24-h radiological predictors for clinical and functional outcomes in stroke patients obtaining complete recanalization in one pass of mechanical thrombectomy (MT) in an optimal baseline and procedural setting. METHODS: A retrospective analysis was conducted of prospectively collected data from 924 stroke patients with anterior large vessel occlusion, Alberta Stroke Program Early Computed Tomography (ASPECT) score ≥6 and pre-stroke modified Rankin Scale score 0, who started MT ≤6 h from symptom onset and obtained first-pass complete recanalization. A first logistic regression model was performed to identify baseline clinical predictors and a second model to identify baseline radiological/procedural predictors. A third model including baseline clinical and radiological/procedural predictors was performed, and a fourth model including independent baseline predictors from the third model plus 24-h radiological variables (hemorrhagic transformation [HT] and cerebral edema [CED]). RESULTS: In the fourth model, higher National Institutes of Health Stroke Scale (NIHSS) score (odds ratio [OR] 1.089) and higher ASPECT score (OR 1.292) were predictors of early neurological improvement (ENI) (NIHSS score ≤4 points from baseline or NIHSS score of 0 at 24 h), whereas older age (OR 0.973), longer procedure time (OR 0.990), HT (OR 0.272) and CED (OR 0.569) were inversely associated with ENI. Older age (OR 0.970), diabetes mellitus (OR 0.456), higher NIHSS score (OR 0.886), general anesthesia (OR 0.454), longer onset-to-groin time (OR 0.996), HT (OR 0.340) and CED (OR 0.361) were inversely associated with 3-month excellent functional outcome (mRS score 0-1), whereas higher ASPECT score (OR 1.294) was a predictor of excellent outcome. CONCLUSIONS: Higher NIHSS score was a predictor of ENI but inversely associated with 3-month excellent outcome. Older age, HT and CED were inversely associated with both good outcomes.

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.

Proposal of multimodal computed tomography-based scoring system in prediction of hemorrhagic transformation in acute ischemic stroke.

INTRODUCTION: The routinely used computed tomography (CT)-based workup in the setting of acute ischemic stroke (AIS) includes non-contrast brain CT, CT angiography (CTA), and CT perfusion. Several CT, CTA, CTP-based radiological biomarkers of hemorrhagic transformation (HT) were reported. AIM OF THE STUDY: To assess the predictive value of the combined multimodal CT parameters for HT after AIS and proposal of predictive scoring scale. METHODS: The source images of the NCCT, CTA and CTP of 282 AIS patients involving the anterior circulation (HT = 91, non-HT = 191) were retrospectively reviewed and the following biomarkers were recorded and analyzed: Early subtle ischemic signs, hyperdense middle cerebral artery sign (HMCAS) and Alberta Stroke Program Early CT Score (ASPECTS) < 7 in NCCT, large-vessel occlusion (LVO), clot burden score (CBS) < 6, large-vessel occlusion, poor collateral score (CS) and Tmax > 6 s ≥ 56.5 ml. A scoring system to predict HT based on these biomarkers was developed. Each biomarker counts for a single point with the total score ranging from 0 to 7. RESULTS: All the aforementioned multimodal CT biomarkers and the selected cut offs were significantly associated with higher HT risk. The calculated scores were statistically significant different between the HT and the non-HT groups with AUC 0.761 (95% CI 0.703-0.819, P < 0.0000001). Rates of HT were approximately five times higher in patients with score ≥ 3. CONCLUSION: Multimodal CT-based scoring system may provide highly reliable predictive model of hemorrhagic transformation in acute ischemic stroke.

Intravenous Thrombolysis 4.5-9 Hours After Stroke Onset: A Cohort Study from the TRISP Collaboration.

OBJECTIVE: To investigate the safety and effectiveness of intravenous thrombolysis (IVT) >4.5-9 hours after stroke onset, and the relevance of advanced neuroimaging for patient selection. METHODS: Prospective multicenter cohort study from the ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration. Outcomes were symptomatic intracranial hemorrhage, poor 3-month functional outcome (modified Rankin scale 3-6) and mortality. We compared: (i) IVT >4.5-9 hours versus 0-4.5 hours after stroke onset and (ii) within the >4.5-9 hours group baseline advanced neuroimaging (computed tomography perfusion, magnetic resonance perfusion or magnetic resonance diffusion-weighted imaging fluid-attenuated inversion recovery) versus non-advanced neuroimaging. RESULTS: Of 15,827 patients, 663 (4.2%) received IVT >4.5-9 hours and 15,164 (95.8%) within 4.5 hours after stroke onset. The main baseline characteristics were evenly distributed between both groups. Time of stroke onset was known in 74.9% of patients treated between >4.5 and 9 hours. Using propensity score weighted binary logistic regression analysis (onset-to-treatment time >4.5-9 hours vs onset-to-treatment time 0-4.5 hours), the probability of symptomatic intracranial hemorrhage (ORadjusted 0.80, 95% CI 0.53-1.17), poor functional outcome (ORadjusted 1.01, 95% CI 0.83-1.22), and mortality (ORadjusted 0.80, 95% CI 0.61-1.04) did not differ significantly between both groups. In patients treated between >4.5 and 9 hours, the use of advanced neuroimaging was associated with a 50% lower mortality compared with non-advanced imaging only (9.9% vs 19.7%; ORadjusted 0.51, 95% CI 0.33-0.79). INTERPRETATION: This study showed no evidence in difference of symptomatic intracranial hemorrhage, poor outcome, and mortality in selected stroke patients treated with IVT between >4.5 and 9 hours after stroke onset compared with those treated within 4.5 hours. Advanced neuroimaging for patient selection was associated with lower mortality. ANN NEUROL 2023;94:309-320.

Mechanical thrombectomy for in-hospital stroke: data from the Italian Registry of Endovascular Treatment in Acute Stroke.

BACKGROUND: The benefit, safety, and time intervals of mechanical thrombectomy (MT) in patients with in-hospital stroke (IHS) are unclear. We sought to evaluate the outcomes and treatment times for IHS patients compared with out-of-hospital stroke (OHS) patients receiving MT. METHODS: We analyzed data from the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) between 2015 and 2019. We compared the functional outcomes (modified Rankin Scale (mRS) scores) at 3 months, recanalization rates, and symptomatic intracranial hemorrhage (sICH) after MT. Time intervals from stroke onset-to-imaging, onset-to-groin, and onset-to-end MT were recorded for both groups, as were door-to-imaging and door-to-groin for OHS. A multivariate analysis was performed. RESULTS: Of 5619 patients, 406 (7.2%) had IHS. At 3 months, IHS patients had a lower rate of mRS 0-2 (39% vs 48%, P<0.001) and higher mortality (30.1% vs 19.6%, P<0.001). Recanalization rates and sICH were similar. Time intervals (min, median (IQR)) from stroke onset-to-imaging, onset-to-groin, and onset-to-end MT were favorable for IHS (60 (34-106) vs 123 (89-188.5); 150 (105-220) vs 220 (168-294); 227 (164-303) vs 293 (230-370); all P<0.001), whereas OHS had lower door-to-imaging and door-to-groin times compared with stroke onset-to-imaging and onset-to-groin for IHS (29 (20-44) vs 60 (34-106), P<0.001; 113 (84-151) vs 150 (105-220); P<0.001). After adjustment, IHS was associated with higher mortality (aOR 1.77, 95% CI 1.33 to 2.35, P<0.001) and a shift towards worse functional outcomes in the ordinal analysis (aOR 1.32, 95% CI 1.06 to 1.66, P=0.015). CONCLUSION: Despite favorable time intervals for MT, IHS patients had worse functional outcomes than OHS patients. Delays in IHS management were detected.

The role of automated computed topography perfusion in prediction of hemorrhagic transformation after acute ischemic stroke.

INTRODUCTION: The role of computed tomography perfusion (CTP) in prediction of hemorrhagic transformation (HT) has been evolving. We aimed to study the role of automated perfusion post-processing software in prediction of HT using the commercially available RAPID software. METHODS: Two hundred eighty-two patients with anterior circulation ischemic stroke, who underwent CTP with RAPID automated post-processing, were retrospectively enrolled and divided into HT (n = 91) and non-HT groups (n = 191). The automated RAPID-generated perfusion maps were reviewed. Mismatch volume and ratio, time to maximum (Tmax) > 4-10s volumes, hypoperfusion index, cerebral blood flow (CBF) < 20-38% volumes, cerebral blood volume (CBV) < 34%-42% volumes, and CBV index were recorded and analyzed. RESULTS: The volumes of brain tissues suffering from reduction of cerebral blood flow (CBF < 20%-38%), reduction in cerebral blood volumes (CBV < 34-42%), and delayed contrast arrival times (Tmax > 4-10s) were significantly higher in the HT group. The mismatch volumes were also higher in the HT group (p = .001). Among these parameters, the Tmax > 6s volume was the most reliable and sensitive predictor of HT (p = .001, AUC = 0.667). However, the combination of the perfusion parameters can slightly improve the diagnostic efficiency (AUC = 0.703). There was no statistically significant difference between the non-HT group and either the parenchymal or the symptomatic subtypes. CONCLUSION: The RAPID automated CTP parameters can provide a reliable predictor of HT overall but not the parenchymal or the symptomatic subtypes. The infarct area involving the penumbra and core represented by the Tmax > 6s threshold is the most sensitive predictor; however, the combination of the perfusion parameters can slightly improve the diagnostic efficiency.

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.

Intravenous Thrombolysis in Patients With Ischemic Stroke Aged ≥90 Years: A Cohort Study From the TRISP Collaboration.

BACKGROUND: The probability to receive intravenous thrombolysis (IVT) for treatment of acute ischemic stroke declines with increasing age and is consequently the lowest in very elderly patients. Safety concerns likely influence individual IVT treatment decisions. Using data from a large IVT registry, we aimed to provide more evidence on safety of IVT in the very elderly. METHODS: In this prospective multicenter study from the TRISP (Thrombolysis in Ischemic Stroke Patients) registry, we compared patients ≥90 years with those <90 years using symptomatic intracranial hemorrhage (ECASS [European Cooperative Acute Stroke Study]-II criteria), death, and poor functional outcome in survivors (modified Rankin Scale score 3-5 for patients with prestroke modified Rankin Scale score ≤2 and modified Rankin Scale score 4-5 for patients prestroke modified Rankin Scale ≥3) at 3 months as outcomes. We calculated adjusted odds ratio with 95% CI using logistic regression models. RESULTS: Of 16 974 eligible patients, 976 (5.7%) were ≥90 years. Patients ≥90 years had higher median National Institutes of Health Stroke Scale on admission (12 versus 8) and were more often dependent prior to the index stroke (prestroke modified Rankin Scale score of ≥3; 45.2% versus 7.4%). Occurrence of symptomatic intracranial hemorrhage (5.7% versus 4.4%, odds ratioadjusted 1.14 [0.83-1.57]) did not differ significantly between both groups. However, the probability of death (odds ratioadjusted 3.77 [3.14-4.53]) and poor functional outcome (odds ratioadjusted 2.63 [2.13-3.25]) was higher in patients aged ≥90 years. Results for the sample of centenarians (n=21) were similar. CONCLUSIONS: The probability of symptomatic intracranial hemorrhage after IVT in very elderly patients with stroke did not exceed that of their younger counterparts. The higher probability of death and poor functional outcome during follow-up in the very elderly seems not to be related to IVT treatment. Very high age itself should not be a reason to withhold IVT.

Endovascular treatment in patients with acute ischemic stroke and cancer: Systematic review and meta-analysis.

Introduction: Although stroke occurs frequently in patients with cancer, there is scarce evidence regarding the safety and efficacy of endovascular treatment (EVT) in patients with acute ischemic stroke and concurrent cancer. We performed a systematic review and meta-analysis to summarize the existing literature. Methods: We searched for English written observational studies reporting data on safety and efficacy of EVT in patients with acute ischemic stroke and concurrent cancer. Outcomes of interest were: functional independence (modified Rankin Scale (mRS) ⩽ 2); mortality at 3 months; rate of successful recanalization (modified Treatment In Cerebral Ischemia (mTICI) 2b or 3); occurrence of any hemorrhagic transformation (both symptomatic and asymptomatic). We pooled data with Maentel-Haenszel model to calculate cumulative odds ratios (ORs). Results: We included seven studies with a total of 4465 patients, of whom 262 (6%) with cancer. We observed various definitions of cancer across included studies. Patients with cancer had less likely mRS⩽2 at 3 months (24% vs 42%, OR = 0.44; 95% CI = 0.32-0.60) and increased probability of death (43% vs 19%, OR = 5.02; 95% CI = 2.90-8.69). There was no difference in successful recanalization (70% vs 75%, OR = 0.84; 95% CI = 0.49-1.44); patients with cancer had increased risk of any intracerebral hemorrhage after treatment (49% vs 34%, OR = 1.95; 95% CI = 1.28-2.96), though not for symptomatic ICH (OR 1.04; 95% CI = 0.59-1.85). Conclusion: Patients with acute ischemic stroke and cancer have similar EVT recanalization but higher probability of functional dependence, death, and any hemorrhagic transformation, though not necessarily symptomatic, compared with patients without cancer. Our results may help communication with patients and carers.

Fibrinogen Depletion Coagulopathy Predicts Major Bleeding After Thrombolysis for Ischemic Stroke: A Multicenter Study.

BACKGROUND: Symptomatic intracerebral hemorrhage (sICH) and major bleeding can be fatal complications of intravenous thrombolysis (IVT) for acute ischemic stroke. We investigated the impact of early fibrinogen depletion after IVT on major bleeding events. METHODS: This multicenter observational prospective cohort study enrolled 1678 consecutive patients receiving IVT for acute ischemic stroke at 6 Italian centers, undergoing fibrinogen concentration assessment at baseline, 2 hours and 6 hours after IVT. Fibrinogen depletion was defined as a reduction below 200 mg/dL after 2 hours from IVT, or as a reduction below 50% of baseline fibrinogen levels after 2 hours from IVT. Main outcomes were (1) sICH (National Institute of Neurological Disorders and Stroke criteria) and (2) major bleeding defined as fatal bleeding, decrease in the hemoglobin level>2 g/dL/>1 unit transfusion, or bleeding at critical site. Additional outcomes were (1) any ICH, (2) any bleeding, (3) fatal ICH, and (4) sICH according to ECASSII definition. Good functional recovery was defined as modified Rankin Scale score 0 to 2 at 3 months. RESULTS: Overall, 1678 patients were included (mean age 72 years, 46% female). sICH (n=116) and major bleeding (n=297) were associated with lower rate of good functional recovery (P<0.001). Despite similar fibrinogen levels at admission, fibrinogen depletion after 2 hours from IVT was more common in people with sICH, major bleeding and all additional bleeding outcomes. In the backward stepwise multivariable logistic regression model, fibrinogen depletion remained a significant predictor of sICH (OR, 1.55 [95% CI, 1.04-2.32]) and major bleeding (OR, 1.36 [95% CI, 1.03-1.8]). Thirty-one percent of sICH could be attributable to fibrinogen depletion. The association between fibrinogen depletion and worse clinical outcome at 3 months after stroke (P=0.012) was attributable to the higher risk of major bleeding/sICH. CONCLUSIONS: Fibrinogen depletion significantly increases the risk of sICH and major bleeding after IVT for acute ischemic stroke. Fibrinogen depletion represents an independent risk factor for bleeding, and routine assessment could be considered to stratify the risk of ICH. Trials on early fibrinogen repletion are needed to investigate mitigation of bleeding risk.

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.

Thrombolysis in stroke patients with elevated inflammatory markers.

OBJECTIVE: To investigate the prognostic value of white blood cell count (WBC) on functional outcome, mortality and bleeding risk in stroke patients treated with intravenous thrombolysis (IVT). METHODS: In this prospective multicenter study from the TRISP registry, we assessed the association between WBC on admission and 3-month poor outcome (modified Rankin Scale 3-6), mortality and occurrence of symptomatic intracranial hemorrhage (sICH; ECASS-II-criteria) in IVT-treated stroke patients. WBC was used as continuous and categorical variable distinguishing leukocytosis (WBC > 10 × 109/l) and leukopenia (WBC < 4 × 109/l). We calculated unadjusted/ adjusted odds ratios with 95% confidence intervals (OR [95% CI]) with logistic regression models. In a subgroup, we analyzed the association of combined leukocytosis and elevated C-reactive protein (CRP > 10 mg/l) on outcomes. RESULTS: Of 10,813 IVT-treated patients, 2527 had leukocytosis, 112 leukopenia and 8174 normal WBC. Increasing WBC (by 1 × 109/l) predicted poor outcome (ORadjusted 1.04[1.02-1.06]) but not mortality and sICH. Leukocytosis was independently associated with poor outcome (ORadjusted 1.48[1.29-1.69]) and mortality (ORadjusted 1.60[1.35-1.89]) but not with sICH (ORadjusted 1.17[0.94-1.45]). Leukopenia did not predict any outcome. In a subgroup, combined leukocytosis and elevated CRP had the strongest association with poor outcome (ORadjusted 2.26[1.76-2.91]) and mortality (ORadjusted 2.43[1.86-3.16]) when compared to combined normal WBC and CRP. CONCLUSION: In IVT-treated patients, leukocytosis independently predicted poor functional outcome and death. Bleeding complications after IVT were not independently associated with leukocytosis.

Evaluation of stroke prognostication using age and NIH Stroke Scale index (SPAN-100 index) in delayed intravenous thrombolysis patients (beyond 4.5 hours).

OBJECTIVES: the efficacy of delayed intravenous tissue plasminogen activator (tPA), beyond the 4.5 h window, is evolving. Advanced age and high admission National Institutes of Health Stroke Scale (NIHSS) score are proposed to adversely affect the outcome of delayed thrombolysis and limit the inclusion criteria. The summation of patient age and admission NIHSS score was introduced as the SPAN-100 index as a tool of prediction of the clinical outcome after acute ischemic stroke (AIS). We aimed to assess the SPAN-100 index in AIS thrombolysed patients after 4.5 h. MATERIALS AND METHODS: The SPAN-100 index was applied to AIS patients receiving delayed IV thrombolysis (IVT) after 4.5 h. Patients demographics, risk factors, clinical, laboratory and radiological data, mismatch evidence, treatment onset and modality, NIHSS score at baseline and at discharge, and 3 months follow-up modified Rankin Scale (mRS) were reviewed. SPAN-100 score ≥ 100 is classified as SPAN-100 positive while score < 100 is SPAN-100 negative. Clinical outcomes, death and intracerebral hemorrhage (ICH) incidences were compared between SPAN-100 positive and negative groups. RESULTS: SPAN-100-positive delayed IVT-patients (11/136) had a 6-fold increased risk for unfavorable outcome compared to SPAN-negative patients (OR 6.34; 95% CI 1.59-25.24 p=0.004), however there was no relation between the SPAN-100 positivity and mortality or ICH. CONCLUSION: SPAN-100-positive patients are more likely to achieve non-favorable outcome with delayed IVT in comparison to the SPAN-100-negative patients. SPAN-100 index may influence the eligibility criteria of delayed thrombolysis.

In-hospital and out-of-hospital stroke in patients with COVID-19: two different diseases?

BACKGROUND: Ischemic stroke is a known complication of COVID-19. It may have a different pathogenesis and worse outcome compared to stroke in patients without COVID-19. Furthermore, patients with COVID-19 and out-of-hospital stroke onset might have different characteristics compared to patients with COVID-19 and in-hospital stroke onset. The aim of our study was to analyze the characteristics of patients with stroke with and without COVID-19 and of patients with COVID-19 with in-hospital and out-of-hospital stroke. METHODS: We performed a retrospective study of all consecutive patients admitted to our hospital with ischemic stroke between October 2020 and February 2021. We compared functional outcome, lab test, demographic, and clinical characteristics between patients with or without COVID-19. We performed a sub-analysis comparing patients with COVID-19 and in-hospital and out-of-hospital stroke onset. RESULTS: We included in the final analysis 137 patients of whom 26 with COVID-19. Half (13) had out-of-hospital stroke and half in-hospital stroke onset. Overall, patients with COVID-19 had higher mortality compared to the control group (27% vs 9%, p: 0.02), and non-significantly lower rate of good functional outcome (50% vs 63%, p: 0.22). Patients with COVID-19 and out-of-hospital stroke had higher rate of good functional outcome (69% vs 39%, p: 0.05), higher lymphocyte count, and lower D-dimer compared with patients with in-hospital stroke onset. CONCLUSIONS: Patients with stroke and COVID-19 had higher mortality compared to patients without COVID-19. Among patients with COVID-19 those with out-of-hospital stroke had better outcome and fewer blood test abnormalities compared to patients with in-hospital stroke.