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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.
Assuntos
Procedimentos Endovasculares , AVC Isquêmico , Sistema de Registros , Trombectomia , Humanos , Masculino , Feminino , Idoso , AVC Isquêmico/cirurgia , AVC Isquêmico/terapia , Pessoa de Meia-Idade , Trombectomia/efeitos adversos , Trombectomia/métodos , Procedimentos Endovasculares/efeitos adversos , Itália , Idoso de 80 Anos ou mais , Estudos de Coortes , Fatores de Tempo , Resultado do Tratamento , Avaliação de Resultados em Cuidados de SaúdeRESUMO
BACKGROUND: Real-world studies on fremanezumab, an anti-calcitonin gene-related peptide monoclonal antibody for migraine prevention, are few and with limited follow-up. OBJECTIVE: We aimed to evaluate the long-term (up to 52 weeks) effectiveness and tolerability of fremanezumab in high-frequency episodic migraine and chronic migraine. METHODS: This s an independent, prospective, multicenter cohort study enrolling outpatients in 17 Italian Headache Centers with high-frequency episodic migraine or chronic migraine and multiple preventive treatment failures. Patients were treated with fremanezumab 225 mg monthly. The primary outcomes included changes from baseline (1 month before treatment) in monthly headache days, response rates (reduction in monthly headache days from baseline), and persistence in medication overuse at months 3, 6, and 12 (all outcome timeframes refer to the stated month). Secondary outcomes included changes from baseline in acute medication intake and disability questionnaires scores at the same timepoints. A last observation carried forward analysis was also performed. RESULTS: A total of 90 patients who received at least one dose of fremanezumab and with a potential 12-month follow-up were included. Among them, 15 (18.0%) patients discontinued treatment for the entire population, a reduction in monthly headache days compared with baseline was reported at month 3, with a significant median [interquartile range] reduction in monthly headache days (- 9.0 [11.5], p < 0.001). A statistically different reduction was also reported at month 6 compared with baseline (- 10.0 [12.0]; p < 0.001) and at 12 months of treatment (- 10.0 [14.0]; p < 0.001). The percentage of patients with medication overuse was significantly reduced compared with baseline from 68.7% (57/83) to 29.6% (24/81), 25.3% (19/75), and 14.7% (10/68) at 3, 6, and 12 months of treatment, respectively (p < 0.001). Acute medication use (days and total number) and disability scores were also significantly reduced (p < 0.001). A ≥ 50% response rate was achieved for 51.9, 67.9, and 76.5% of all patients at 3, 6, and 12 months, respectively. Last observation carried forward analyses confirmed these findings. Fremanezumab was well tolerated, with just one patient discontinuing treatment because of adverse events. CONCLUSIONS: This study provides evidence for the real-world effectiveness of fremanezumab in treating both high-frequency episodic migraine and chronic migraine, with meaningful and sustained improvements in multiple migraine-related variables. No new safety issue was identified.
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Transtornos de Enxaqueca , Uso Excessivo de Medicamentos Prescritos , Humanos , Estudos de Coortes , Estudos Prospectivos , Resultado do Tratamento , Método Duplo-Cego , Transtornos de Enxaqueca/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Cefaleia/tratamento farmacológicoRESUMO
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.
Assuntos
Edema Encefálico , Isquemia Encefálica , Diabetes Mellitus , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Estudos de Coortes , Edema Encefálico/etiologia , Trombectomia/métodos , Resultado do Tratamento , Estudos Retrospectivos , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Procedimentos Endovasculares/métodosRESUMO
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.
Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , Insuficiência Cardíaca , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , AVC Isquêmico/etiologia , Trombectomia/efeitos adversos , Resultado do Tratamento , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/cirurgia , Insuficiência Cardíaca/complicações , Sistema de Registros , Estudos Retrospectivos , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/epidemiologia , Procedimentos Endovasculares/efeitos adversosRESUMO
Introduction: Recent anticoagulant intake represents a contraindication for thrombolysis in acute ischemic stroke. Idarucizumab reverses the anticoagulant effect of dabigatran, potentially allowing for thrombolysis. This nation-wide observational cohort study, systematic review, and meta-analysis evaluated the efficacy and safety of thrombolysis preceded by dabigatran-reversal in people with acute ischemic stroke. Patients and methods: We recruited people undergoing thrombolysis following dabigatran-reversal at 17 stroke centers in Italy (reversal-group), people on dabigatran treated with thrombolysis without reversal (no-reversal group), and age, sex, hypertension, stroke severity, and reperfusion treatment-matched controls in 1:7 ratio (control-group). We compared groups for symptomatic intracranial hemorrhage (sICH, main outcome), any brain hemorrhage, good functional outcome (mRS 0-2 at 3 months), and death. The systematic review followed a predefined protocol (CRD42017060274), and odds ratio (OR) meta-analysis was implemented to compare groups. Results: Thirty-nine patients in dabigatran-reversal group and 300 matched controls were included. Reversal was associated with a non-significant increase in sICH (10.3% vs 6%, aOR = 1.32, 95% CI = 0.39-4.52), death (17.9% vs 10%, aOR = 0.77, 95% CI = 0.12-4.93) and good functional outcome (64.1% vs 52.8%, aOR = 1.41, 95% CI = 0.63-3.19). No hemorrhagic events or deaths were registered in no-reversal group (n = 12). Pooling data from 3 studies after systematic review (n = 1879), reversal carried a non-significant trend for sICH (OR = 1.53, 95% CI = 0.67-3.50), death (OR = 1.53, 95% CI = 0.73-3.24) and good functional outcome (OR = 2.46, 95% CI = 0.85-7.16). Discussion and conclusion: People treated with reperfusion strategies after dabigatran reversal with idarucizumab seem to have a marginal increase in the risk of sICH but comparable functional recovery to matched patients with stroke. Further studies are needed to define treatment cost-effectiveness and potential thresholds in plasma dabigatran concentration for reversal.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Dabigatrana/efeitos adversos , Antitrombinas/efeitos adversos , AVC Isquêmico/complicações , Isquemia Encefálica/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Acidente Vascular Cerebral/tratamento farmacológico , Anticoagulantes/uso terapêutico , Hemorragias Intracranianas/induzido quimicamente , Estudos Observacionais como Assunto , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Randomized controlled trials (RCTs) proved that short-term (21-90 days) dual antiplatelet therapy (DAPT) reduces the risk of early ischemic recurrences after a noncardioembolic minor stroke or high-risk transient ischemic attack (TIA) without substantially increasing the hemorrhagic risk. We aimed at understanding whether and how real-world use of DAPT differs from RCTs. METHODS: READAPT (Real-Life Study on Short-Term Dual Antiplatelet Treatment in Patients With Ischemic Stroke or TIA) is a prospective cohort study including >18-year-old patients treated with DAPT after a noncardioembolic minor ischemic stroke or high-risk TIA from 51 Italian centers. The study comprises a 90-day follow-up from symptom onset. In the present work, we reported descriptive statistics of baseline data of patients recruited up to July 31, 2022, and proportions of patients who would have been excluded from RCTs. We compared categorical data through the χ² test. RESULTS: We evaluated 1070 patients, who had 72 (interquartile range, 62-79) years median age, were mostly Caucasian (1045; 97.7%), and were men (711; 66.4%). Among the 726 (67.9%) patients with ischemic stroke, 226 (31.1%) did not meet the RCT inclusion criteria because of National Institutes of Health Stroke Scale score >3 and 50 (6.9%) because of National Institutes of Health Stroke Scale score >5. Among the 344 (32.1%) patients with TIA, 69 (19.7%) did not meet the RCT criteria because of age, blood pressure, clinical features, duration of TIA, presence of diabetes score <4 and 252 (74.7%) because of age, blood pressure, clinical features, duration of TIA, presence of diabetes score <6 and no symptomatic arterial stenosis. Additionally, 144 (13.5%) patients would have been excluded because of revascularization procedures. Three hundred forty-five patients (32.2%) did not follow the RCT procedures because of late (>24 hours) DAPT initiation; 776 (72.5%) and 676 (63.2%) patients did not take loading doses of aspirin and clopidogrel, respectively. Overall, 84 (7.8%) patients met the RCT inclusion/exclusion criteria. CONCLUSIONS: The real-world use of DAPT is broader than RCTs. Most patients did not meet the RCT criteria because of the severity of ischemic stroke, lower risk of TIA, late DAPT start, or lack of antiplatelet loading dose. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05476081.
Assuntos
Ataque Isquêmico Transitório , AVC Isquêmico , Acidente Vascular Cerebral , Adolescente , Feminino , Humanos , Masculino , Quimioterapia Combinada , Ataque Isquêmico Transitório/tratamento farmacológico , AVC Isquêmico/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológicoRESUMO
BACKGROUND: The differential diagnosis of frontotemporal dementia (FTD) is still a challenging task due to its symptomatic overlap with other neurological diseases and the lack of biofluid-based biomarkers. OBJECTIVE: To investigate the diagnostic potential of a combination of novel biomarkers in cerebrospinal fluid (CSF) and blood. METHODS: We included 135 patients from the Center for Memory Disturbances, University of Perugia, with the diagnoses FTD (nâ=â37), mild cognitive impairment due to Alzheimer's disease (MCI-AD, nâ=â47), Lewy body dementia (PDD/DLB, nâ=â22), and cognitively unimpaired patients as controls (OND, nâ=â29). Biomarker levels of neuronal pentraxin-2 (NPTX2), neuronal pentraxin receptor, neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were measured in CSF, as well as NfL and GFAP in serum. We assessed biomarker differences by analysis of covariance and generalized linear models (GLM). We performed receiver operating characteristics analyses and Spearman correlation to determine biomarker associations. RESULTS: CSF NPTX2 and serum GFAP levels varied most between diagnostic groups. The combination of CSF NPTX2, serum NfL and serum GFAP differentiated FTD from the other groups with good accuracy (FTD versus MCI-AD: area under the curve (AUC) [95% CI]â=â0.89 [0.81-0.96]; FTD versus PDD/DLB: AUCâ=â0.82 [0.71-0.93]; FTD versus OND: AUCâ=â0.80 [0.70-0.91]). CSF NPTX2 and serum GFAP correlated positively only in PDD/DLB (ρ=â0.56, pâ<â0.05). NPTX2 and serum NfL did not correlate in any of the diagnostic groups. Serum GFAP and serum NfL correlated positively in all groups (ρ=â0.47-0.74, pâ<â0.05). CONCLUSION: We show the combined potential of CSF NPTX2, serum NfL, and serum GFAP to differentiate FTD from other neurodegenerative disorders.
Assuntos
Doença de Alzheimer , Demência Frontotemporal , Doença por Corpos de Lewy , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Demência Frontotemporal/diagnóstico , Demência Frontotemporal/líquido cefalorraquidiano , Proteína Glial Fibrilar Ácida , Filamentos Intermediários , Doença por Corpos de Lewy/líquido cefalorraquidiano , Proteínas de Neurofilamentos , Proteínas tau/líquido cefalorraquidianoRESUMO
Stroke is defined as an acute cerebrovascular accident characterized by an interruption of vascular supply lasting more than 24 hours. Therapeutic goal, reassumed at the well-known "time is brain", is strictly focused on achieving timely restoration of cerebral blood flow at risk of infarction to reduce neurological complications. Consequently, time to treatment is the most important determinant of the efficacy of reperfusion. Current guidelines strongly recommend the use of intravenous thrombolysis with tissue plasminogen activator and endovascular thrombectomy to reach that goal. These therapies allow to obtain 1.9 million neurons saved per each minute of onset-to-reperfusion time and 4.2 days of extra healthy life and are crucial in the reduction of mortality and morbidity of ischemic stroke. Multidisciplinary collaboration involving a coordinated prehospital management and stroke team composed of physicians with expertise in emergency medicine, neurologists, radiologists, nurses, technicians, and laboratory personnel are essential for rapid triage and should guide clinical decisions to deliver the appropriate reperfusion therapy for each patient.
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The clinical diagnosis of Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) is challenging due to highly variable clinical presentation and clinical and pathological overlap with other neurodegenerative diseases. Since cerebrospinal fluid (CSF) mirrors the pathological changes taking place in the brain, it represents a promising source of biomarkers. With respect to classical AD biomarkers, low CSF Aß42 levels have shown a robust prognostic value in terms of development of cognitive impairment in PD and DLB. In the differential diagnosis between AD and DLB, a potential role of t-tau, p-tau and Aß42/Aß38 ratio has been demonstrated. Regarding CSF α-synuclein (α-syn) species, lower levels of total α-synuclein (t-α-syn) and higher concentration of oligomeric-α-synuclein (o-α-syn) and phosphorylated α-synuclein (p-α-syn) have been observed in PD. Furthermore, the detection of "pro-aggregating" α-synuclein has enabled the discrimination of patients affected by synucleinopathies with high sensitivity and specificity. New promising biomarkers are emerging: GCase activity (reduced in PD and DLB patients vs. controls), CSF/serum albumin ratio (increased in PD and DLB), fatty-acid-binding protein (increased in AD and DLB vs. PD), visinin-like protein-1 (increased in AD vs. DLB) and monoamines (useful in differential diagnosis among PD and DLB). These encouraging results need to be confirmed by future studies.
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Biomarcadores/líquido cefalorraquidiano , Doença por Corpos de Lewy/diagnóstico , Doença de Parkinson/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Diagnóstico Diferencial , Humanos , alfa-Sinucleína/líquido cefalorraquidianoAssuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Fragmentos de Peptídeos/líquido cefalorraquidiano , alfa-Sinucleína/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Diagnóstico Diferencial , Humanos , Filamentos Intermediários/metabolismo , Doença por Corpos de Lewy/diagnóstico , PrognósticoRESUMO
The variability of Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers (Aß42, t-Tau and p-Tau) undermines their full-fledged introduction into routine diagnostics and clinical trials. The introduction of automatic systems can improve the diagnostic performance promoting standardization and reducing the impact of preanalytical and analytical factors. Here we assessed the diagnostic performance of a fully automated chemiluminescent enzyme assay (LUMIPULSE) and compared it with that obtained by using the classical manual enzyme-linked immunosorbent assays (ELISAs). Patients were clinically diagnosed as AD (nâ¯=â¯42) and non-AD (nâ¯=â¯38). Clinical diagnosis was confirmed at follow-up. LUMIPULSE Aß42 was reduced in AD (969.4⯱â¯329.6â¯pg/mL vs. 1625.9⯱â¯745.9â¯pg/mL, pâ¯<0.001), whereas LUMIPULSE t-Tau was increased in AD (768.2⯱â¯281.0â¯pg/mL vs. 337.5⯱â¯159.1â¯pg/mL, pâ¯<â¯0.001) compared to non-AD patients. Both LUMIPULSE Aß42 (AUCâ¯=â¯0.78, spec. = 0.74, sens. = 0.76) and t-Tau (AUCâ¯=â¯0.94, spec. = 0.93, sens. = 0.87) showed good accuracy in distinguish AD from non-AD and a high correlation with the manual ELISAs (râ¯=â¯0.87, pâ¯<â¯0.001 and râ¯=â¯0.92, pâ¯<â¯0.001, respectively). LUMIPULSE improves clinical accuracy in AD diagnosis, promoting the use of standardized values for CSF biomarkers with a good correlation with classical manual assays.