Thrombectomy in ischemic stroke patients with tandem occlusion in the posterior versus anterior circulation.

BACKGROUND: Mechanical thrombectomy (MT) was found to be beneficial in acute ischemic stroke patients with anterior tandem occlusion (a-TO). Instead, little is known about the effectiveness of MT in stroke patients with posterior tandem occlusion (p-TO). We aimed to compare MT within 24 h from last known well time in ischemic stroke patients with p-TO versus a-TO. METHODS: We conducted a cohort study on prospectively collected data of patients registered in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) who were treated with MT within 24 h from last known well time for acute ischemic stroke with p-TO (n = 275) or a-TO (n = 1853). RESULTS: After adjustment for unbalanced pre-procedure variables (year 2015-2021, age, sex, NIHSS score, ASPECTS, and time strata for puncture groin) and pre-stroke mRS score as pre-defined predictor, p-TO was significantly associated with lower probability of mRS score 0-2 (OR 0.415, 95% CI 0.268-0.644) and with higher risk of death (OR 2.813, 95% CI 2.080-3.805) at 3 months. After adjustment for unbalanced procedural and post-procedure variables (IVT, general anesthesia, TICI 3, and 24-h HT) and pre-stroke mRS score as pre-defined predictor, association between p-TO and lower probability of mRS score 0-2 (OR 0.444, 95% CI 0.304-0.649) and association between p-TO and with higher risk of death (OR 2.971, 95% CI 1.993-4.429) remained significant. CONCLUSIONS: MT within 24 h from last known well time in ischemic stroke patients with p-TO versus a-TO was associated with worse outcomes at 3 months.

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.

The "SALPARE study" of spontaneous intracerebral hemorrhage: part 1.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) is a devastating type of stroke with a huge impact on patients and families. Expanded use of oral anticoagulants and ageing population might contribute to an epidemiological change. In view of these trends, we planned a study to obtain a contemporary picture and identify early prognostic factors to improve secondary prevention. METHODS: This multicenter prospective cohort study included consecutive adult patients with non-traumatic ICH admitted to three academic Italian hospitals (Salerno, Padova, Reggio Emilia) over a 2-year period. Demographic characteristics, vascular risk profile, clinical data and main radiological characteristics were correlated to 90-day clinical outcome. RESULTS: Out of 682 patients [mean age: 73 ± 14 years; 316 (46.3%) females] enrolled in this study, 40% died [86/180 (47.8%) in Salerno, 120/320 (37.5%) in Padova, 67/182 (36.8%) in Reggio Emilia; p < 0.05)] and 36% were severely disabled at 90 days. Several factors were associated with a higher risk of poor functional outcome such as antithrombotic drug use, hyperglycemia, previous cerebrovascular accident, low platelet count, and pontine/massive/intraventricular hemorrhage. However, at multivariate analysis only pre-ICH mRS score (OR 30.84), GCS score at presentation (OR 11.88), initial hematoma volume (OR 29.71), and NIHSS score at presentation (OR 25.89) were independent predictors of death and poor functional outcome. CONCLUSION: Despite the heterogeneity among centers, this study on ICH has identified four simple prognostic factors that can independently predict patients outcome, stratify their risk, and guide their management.

The "SALPARE study" of spontaneous intracerebral haemorrhage-part 2-early CT predictors of outcome in ICH: keeping it simple.

BACKGROUND: The aim of this study was to investigate the prognostic role of hematoma characteristics and hematoma expansion (HE) in patients with spontaneous intracerebral hemorrhage (ICH). METHODS: This multicenter prospective cohort study enrolled consecutive adult patients with non-traumatic ICH admitted to three Italian academic hospitals (Salerno, Padova, Reggio Emilia) over a 2-year period. Early noncontrast CT (NCCT) features of the hematoma, including markers of HE, and 3-month outcome were recorded. Multivariable logistic regression analysis was performed to identify predictors of poor outcome. RESULTS: A total of 682 patients were included in the study [mean age: 73 ± 14 years; 316 (46.3%) females]. Pontine and massive hemorrhage, intraventricular bleeding, baseline hematoma volume > 15 mL, blend sign, swirl sign, margin irregularity ≥ 4, density heterogeneity ≥ 3, hypodensity ≥ 1, island sign, satellite sign, and black hole sign were associated with a higher risk of mortality and disability. However, at multivariate analysis only initial hematoma volume (OR 29.71) proved to be an independent predictor of poor functional outcome at 3 months. CONCLUSION: Simple hematoma volume measured on baseline CT best identifies patients with a worse outcome, while early NCCT markers of HE do not seem to add any clinically significant information.

Trends of recanalization therapies and state of art for ischemic stroke treatment in Campania region, Italy.

BACKGROUND: According to the last Italian report by the Ministry of Health in 2018, the estimated number of acute ischemic strokes (AIS) in Campania is 10,000/year, with an expected number of 1390 intravenous thrombolysis (IVT) and 694 mechanical thrombectomies (MT). In 2017, only 1.5% of expected patients received IVT and 0.2% MT. This study analyzed the trend of IVT and MT in 2019-2020 and depicted the state of art of Stroke Care in Campania. METHODS: From the regional health task force, we obtained the hospital discharge forms from all private and public hospitals in Campania; we selected patients with a principal diagnosis of AIS and measured the rate of patients admitted to neurology units and the rate of IVT, MT, and IVT + MT for both 2019 and 2020. RESULTS: In 2019, we observed 4817 admissions for AIS; 2858/4817 (59.3%) patients were admitted to neurology units. Out of 4817 patients, 192 received IVT, 165 MT, and 131 IVT + MT (488 treated patients; 10.1%). In 2020, we observed 4129 admissions for AIS; 2502/4129 (62.7%) patients were admitted to neurology units. Out of 4129 patients, 198 received IVT, 250 MT, and 180 IVT + MT (628 treated patients; 15.2%). These results showed that despite a reduction of AIS admissions in 2020, the relative and absolute rate of recanalization treatments increased. However, the number of patients who were not admitted to neurology units nor received acute treatments remained dramatically high. CONCLUSION: Despite the development of acute treatments, the Campania Stroke Network still needs significative efforts to improve.

Importance of Echocardiography and Clinical "Red Flags" in Guiding Genetic Screening for Fabry Disease.

Introduction: Aim of this study was to evaluate, in a metropolitan area not already explored, the prevalence of Anderson-Fabry disease, by genetic screening, in patients with echocardiographic evidence of left ventricular hypertrophy (LVH) of unknown origin and "clinical red flags". Methods: From August 2016 to October 2017, all consecutive patients referring to our echo-lab for daily hospital practices with echocardiographic evidence of LVH of unknown origin in association with history of at least one of the classical signs and symptoms related to Fabry disease (FD) (neuropathic pain, anhidrosis/hypohidrosis, angiokeratomas, gastrointestinal problems, chronic kidney disease, or cerebrovascular complications) were considered eligible for the FD genetic screening program. Through dried blood spot testing, α-Galactosidase A (α-Gal A) activity and analysis of the GLA gene were performed. Results: Among 3,360 patients who underwent transthoracic echocardiography in our echo-lab during the study period, 30 patients (0.89%; 19 men, mean age 58 ± 18.2 years) were selected. FD was diagnosed in 3 (10%) unrelated patients. Three different GLA gene mutations were detected, one of them [mutation c.388A > G (p.Lys130Glu) in exon 3] never described before. Moreover, probands' familiar genetic screening allowed the identification of 5 other subjects affected by FD. Conclusion: In a metropolitan area not previously investigated, among patients with LVH of unknown origin associated with other "red flags," undergoing genetic screening, the prevalence of FD was very high (10%). Our results highlight the importance of an echocardiographic- and clinical-oriented genetic screening for FD in patients with uncommon cause of LVH.

Acute ischemic stroke with cervical internal carotid artery steno-occlusive lesion: multicenter analysis of endovascular approaches.

BACKGROUND: Occlusion of the internal carotid artery (ICA), whether isolated or in the setting of a tandem lesion (TL) have a poor response to treatment with intravenous thrombolysis. Previous studies ​​have demonstrated the superiority of mechanical thrombectomy in the treatment of acute ischemic stroke (AIS) following large vessel occlusion, compared to standard intravenous fibrinolysis. The aim of our study was to describe endovascular treatment (EVT) in AIS due to isolated ICA occlusion or TL. METHODS: We assessed the association between 90-day outcome and clinical, demographic, imaging, and procedure data in 51 consecutive patients with acute isolated ICA occlusion or TL who underwent EVT. We evaluated baseline NIHSS and mRS, ASPECTS, type of occlusion, stent placement, use of stent retrievers and/or thromboaspiration, duration of the procedure, mTICI, postprocedural therapy and complications. RESULTS: A favorable 90-day outcome (mRS 0-2) was achieved in 34 patients (67 %) and was significantly associated with the use of dual antiplatelet therapy after the procedure (p = 0.008), shorter procedure duration (p = 0.031), TICI 2b-3 (p < 0.001) and lack of post-procedural hemorrhagic transformation (p = 0.001). Four patients did not survive, resulting in a mortality rate of 8 %. CONCLUSIONS: Our study has shown that EVT in the treatment of AIS due to ICA occlusion is safe, and effective in determining a good functional outcome. ICA stenting led to good angiographic results and therapy with a glycoprotein IIb / IIIa inhibitor immediately after stent release did not result in a greater risk of hemorrhage. The use of post-procedural dual antiplatelet therapy was associated with favorable outcome, without a significant increase in hemorrhagic transformation.

A case report of takotsubo syndrome complicated by ischaemic stroke: the clinical dilemma of anticoagulation.

BACKGROUND: Takotsubo syndrome (TTS) is an acute and transient heart failure syndrome due to reversible myocardial dysfunction characterized by a wide spectrum of possible clinical scenarios. About one-fifth of TTS patients experience adverse in-hospital events. Thromboembolic complications, especially stroke, have been reported, albeit in a minority of patients. CASE SUMMARY: A 69-year-old woman presented to our emergency department for dyspnoea after a family quarrel. Electrocardiogram revealed ST-segment elevation in anterolateral leads and laboratory exams showed a slight elevation of high-sensitivity cardiac troponin. The patient was treated according to current guidelines on ST-elevation myocardial infarction and referred to the cath lab. Urgent coronary angiography revealed normal coronary arteries. Based on the patient profile and instrumental findings, a diagnosis of TTS was hypothesized. After 6 days, the patient developed dysarthria and right hemiparesis under therapy with aspirin, whilst low molecular weight heparin had been previously withdrawn. Transthoracic echocardiography (TTE) revealed persisting apical akinesia and a subtle intraventricular thrombus. Head computed tomography and magnetic resonance imaging detected focal areas of ischaemic necrosis resembling diffuse cardioembolic lesions. Anticoagulation therapy was started and regular TTE showed complete recovery of myocardial systolic function and absence of ventricular thrombi at 1-month follow-up. The patient fully recovered speech after 5 months. DISCUSSION: This challenging case reinforces current recommendations to administer antithrombotic therapy in TTS patients with extensive apical dysfunction up to complete or near-complete recovery of myocardial contractility, regardless of the presence of atrial fibrillation, and highlights the importance of close TTE monitoring during the acute phase.

The Impact of Covid-19 Lockdown on Stroke Admissions and Treatments in Campania.

OBJECTIVES: The enforcement of complete lockdown with home confinement has been necessary to limit SARS-CoV-2 contagions in Italy, one the most affected countries worldwide. Simultaneously, in several Emergency Departments, a reduction in cardio- and cerebrovascular presentations was noticed. This study analyses the impact of Covid-19 pandemic and lockdown measures on the incidence of stroke, in Campania, the most densely-populated region in Italy. MATERIALS AND METHODS: We retrospectively analyzed data regarding acute stroke patients presenting at 5 Campania stroke hubs, before and after the issue of lockdown in Italy on March 9th, 2020. RESULTS: Compared to the pre-lockdown, we observed a significant reduction in the number of acute reperfusion treatments in stroke (P for interact 0.001); however the global number of patients presenting with acute stroke did not significantly differ. The time to reach medical attention was significantly longer in the lockdown phase (230 versus 154 min, P 0.016). For patients who underwent acute reperfusion treatment we also observed significantly longer time-to-imaging (30 versus 40 min, P 0.0005) and a trend to longer time-to-needle (75 versus 90 min P 0.23), but not time-to-groin. CONCLUSIONS: This study showed the reduction in acute reperfusion treatments for acute ischemic stroke and the slowdown of stroke pathways, during the lockdown phase of Covid-19 pandemic, in Campania, the third-most-populous and the most-densely populated Italian Region. In the next future, the risk for high-grade disability and death, due to delayed or even avoided hospital presentation due to fear of contagion, may be high.

ADAPT with New Catalyst 5 Reperfusion Catheter for Distal M2 Ischemic Stroke: Preliminary Experience.

OBJECTIVE: We sought to assess preliminary technical and clinical outcomes of Catalyst 5 (CAT 5) as front-line aspiration treatment for M2-M3 occlusion in acute ischemic stroke. METHODS: Patients with symptomatic stroke and distal M2 or M3 occlusions were enrolled retrospectively. A direct aspiration first-pass technique was used as the first treatment option for absolute contraindication to intravenous fibrinolytic therapy. Time to recanalization, first attempt recanalization, and number of attempts were recorded. Successful recanalization was defined as a modified thrombolysis in cerebral infarction score ≥2b; incidence of procedure-related complications was recorded. National Institutes of Health Stroke Scale at discharge and modified Rankin Scale score at 90 days were evaluated by a dedicated neurologist. RESULTS: A total of 11 acute occlusions of distal M2-M3 segment were treated with a direct aspiration first-pass technique using CAT 5 (mean age 69.3 years). Tandem occlusion was present in 2 cases. Intracranial preocclusive mean vessel diameter was 1.9 mm. Overall modified thrombolysis in cerebral infarction score ≥2b was obtained in 72.7% of patients with mean time to recanalization of 36.4 minutes and a mean of 1.9 attempts. First-attempt recanalization with CAT 5 was obtained in 54% of patients with a mean time to recanalization of 29.2 minutes. A stent retriever with proximal aspiration was incorporated as a rescue device in 2 cases. Embolization of new territories was reported after CAT 5 aspiration in 1 patient. No intracranial hemorrhage was detected on follow-up computed tomography. The median National Institutes of Health Stroke Scale score at discharge was 3. At 90 days, a modified Rankin Scale score of 0-2 was achieved in 90.9% of patients. CONCLUSIONS: Preliminary experience using CAT 5 in distal occlusions demonstrates that it may be safe and effective in acute stroke treatment.

Mutations in the GLA Gene and LysoGb3: Is It Really Anderson-Fabry Disease?

Anderson-Fabry disease (FD) is a rare, progressive, multisystem storage disorder caused by the partial or total deficit of the lysosomal enzyme α-galactosidase A (α-Gal A). It is an X-linked, lysosomal enzymopathy due to mutations in the galactosidase alpha gene (GLA), encoding the α-Gal A. To date, more than 900 mutations in this gene have been described. In our laboratories, the study of genetic and enzymatic alterations related to FD was performed in about 17,000 subjects with a symptomatology referable to this disorder. The accumulation of globotriaosylsphingosine (LysoGb3) was determined in blood of positives. Exonic mutations in the GLA gene were detected in 471 patients (207 Probands and 264 relatives): 71.6% of mutations were associated with the classic phenotype, 19.8% were associated with the late-onset phenotype, and 8.6% of genetic variants were of unknown significance (GVUS). The accumulation of LysoGb3 was found in all male patients with a mutation responsible for classic or late-onset FD. LysoGb3 levels were consistent with the type of mutations and the symptomatology of patients. α-Gal A activity in these patients is absent or dramatically reduced. In recent years, confusion about the pathogenicity of some mutations led to an association between non-causative mutations and FD. Our study shows that the identification of FD patients is possible by associating clinical history, GLA gene analysis, α-Gal A assay, and blood accumulation of LysoGB3. In our experience, LysoGB3 can be considered a reliable marker, which is very useful to confirm the diagnosis of Fabry disease.

Multiple sclerosis: relapses and timing of remissions.

BACKGROUND: Relapse is a relatively sudden worsening of neurological status in multiple sclerosis patients. The aim of this paper is to describe the frequency and timing of the subsequent clinical remission, and factors linked to a possible lack of recovery. METHODS: Two hundred and twenty-three relapses in 62 multiple sclerosis patients were examined retrospectively. Kurtzke's Expanded Disability Status Scale (EDSS) scores were calculated every 3 months from 1 year before to 1 year after. Remission was defined as improvement vs. the EDSS as scored during the relapse. Recovery was defined as return to the EDSS as scored before the relapse. RESULTS: The frequency of improvement was 78% at 3 months, 86% at 6, and lower in males (65 vs. 81%). The frequency of recovery was 55% at 3 months, 71% at 6. Kaplan-Meier curves showed stabilization after 6 months, with improvement in 90% of patients, 100% without further relapses. Relapses without recovery were only 30%; 15% excluding short-term relapses. CONCLUSIONS: Incomplete remissions do not appear to be linked to the evolution of the relapse, but to further relapses in the following months; in other words, to the short-term relapse rate.