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BACKGROUND AND AIMS: The relationship between primary biliary cholangitis (PBC) and metabolic dysfunction-associated steatotic liver disease, and its impact on treatment response and prognosis, remains underexplored. METHODS: Patient cohort from two centres comprising long-term follow-up data. All patients had histologically confirmed PBC. Biopsies were classified according to Non-Alcoholic Steatohepatitis Clinical Research Network. Diagnosis of metabolic dysfunction-associated steatotic liver disease was established when steatosis exceeded 5%, along with at least one metabolic risk factor. Patients with specific aetiologies of steatosis, other liver diseases, incomplete results and inadequate treatment with ursodeoxycholic acid were excluded. Data from patients initiating second-line treatment were censored. Treatment response was assessed using the Toronto, Paris II and AST-to-platelet at 12-month criteria. The UK PBC and Globe scores, and liver events were utilized as outcome measures. RESULTS: The study included 129 patients, 36 showing histologically confirmed overlap between PBC and steatosis. Patients with overlap showed worse prognosis according to Paris II (61.1% vs. 33.3%, p = 0.004), Toronto (52.5% vs. 24.7%, p = 0.002), AST-to-platelet 12-month >0.54 (36.1% vs. 17.2%, p = 0.021), Globe >0.30 (49.2% vs. 29.2%, p = 0.033) and UK PBC at 5, 10 and 15 years (p ≤ 0.001). Liver-related mortality and liver transplant were more prevalent in the overlap group (p = 0.001). In the multivariate analysis, steatosis, dyslipidaemia and advanced fibrosis were independently associated to worse outcomes. CONCLUSIONS: Our findings suggest that metabolic dysfunction-associated steatotic liver disease worsens the prognosis of PBC.
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Cirrosis Hepática Biliar , Humanos , Femenino , Masculino , Persona de Mediana Edad , Cirrosis Hepática Biliar/complicaciones , Anciano , Pronóstico , Ácido Ursodesoxicólico/uso terapéutico , Hígado Graso/complicaciones , Resultado del Tratamiento , Factores de Riesgo , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Adulto , Estudios Retrospectivos , Estudios de CohortesRESUMEN
BACKGROUND: The impact of thrombolytics directed towards different thrombus components regarding site of occlusion in combination with mechanical thrombectomy (MT) to achieve endovascular complete recanalization is unclear. METHODS: Retrospective analysis of a prospective database in two stroke centers. Intracranial thrombi retrieved by MT were analyzed using hematoxylin-eosin staining for fibrin and red blood cell proportions, and CD61 immunostaining for platelets proportion in thrombus (PLTPT) assessment. Thrombi composition, baseline variables, etiology, treatment features and occlusion location were analyzed. RESULTS: Overall, 221 patients completed the per protocol analysis and 110 cases achieved a final expanded Thrombolysis in Cerebral Infarction (eTICI) 3 (49%) of which 70 were MT (32%) by first pass effect (FPE). Thrombi from medium distal vessel occlusions had higher PLTPT compared with thrombi from proximal large vessel occlusions (68% vs 61%, P=0.026). In particular, middle cerebral artery M2-M3 segment thrombi had the highest PLTPT (70%), and basilar artery thrombi the lowest PLTPT (41%). After logistic regression analysis adjusted for occlusion location and intravenous fibrinolysis, lower baseline National Institutes of Health Stroke Scale score (adjusted OR (aOR) 0.95, 95% CI 0.913 to 0.998) and PLTPT (aOR 0.97, 95% CI 0.963 to 0.993) were independently associated with FPE. Fewer MT passes (aOR 0.67, 95% CI 0.538 to 0.842) and platelet poor thrombus (<62% PLTPT; aOR 2.39, 95% CI 1.288 to 4.440) were independently associated with final eTICI 3. CONCLUSIONS: Occlusion location might be a surrogate parameter for thrombus composition. Platelet poor clots and fewer MT passes were independently associated with complete endovascular recanalization. Clinical trials testing the benefits of combining selective intra-arterial platelet antagonists with MT to improve endovascular outcomes are warranted.
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We present the case of a 64-year-old female with personal history of breast carcinoma diagnosed in 2011, treated and discharged from the Oncology service after 10 years disease-free who, 21 years after the diagnosis, undergoes a colonoscopy with biopsy sampling due to a 2-year period of diarrhea and weight loss, which histological study show infiltration of the large intestine's by breast carcinoma. Due to the usual lymphatic widespread, metastases of breast cancer in the gastrointestinal tract are extremely rare with nonspecific symptoms, long latency periods and poor prognosis.
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Background: Circadian variations in the timing of the onset of stroke symptoms have been described, showing a morning excess of cardiovascular risk. To date, no differences have been found between stroke subtype and time distribution throughout the day. The present study aims to compare the seasonal and circadian rhythm of symptoms onset in ischemic, hemorrhagic, and stroke mimic patients. Methods: This study was conducted prospectively at a hospital and involved a cohort of stroke alert patients from 2018 to 2021. Stroke subtypes were classified as ischemic stroke, intracerebral hemorrhage (ICH), transient ischemic attack (TIA), and stroke mimic. Clinical variables were recorded, and each patient was assigned to a 4-h interval of the day according to the time of onset of symptoms; unwitnessed stroke patients were analyzed separately. Seasonal changes in stroke distribution were analyzed at 3-month intervals. Results: A total of 2,348 patients were included in this analysis (ischemic 67%, ICH 13%, mimic 16%, and TIA 3%). Regardless of stroke subtype, most of the patients were distributed between 08-12 h and 12-16 h. Significant differences were found in the time distribution depending on stroke subtype, with ICH predominating in the 4-8 h period (dawn), most of which were hypertensive, TIA in the 12-16 h period (afternoon), and stroke mimic in the 20 h period (evening). The ischemic stroke was evenly distributed throughout the different periods of the day. There were no differences in the seasonal pattern between different stroke subtypes, with winter being the one that accumulated the most cases. Conclusion: The present study showed different circadian patterns of stroke subtypes, with a predominance of ICH at dawn and stroke mimic in the afternoon. The stroke circadian rhythm resembles previous studies, with a higher incidence in the morning and a second peak in the afternoon.
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BACKGROUND: Due to the rarity of cerebral venous thrombosis (CVT), performing high-quality scientific research in this field is challenging. Providing answers to unresolved research questions will improve prevention, diagnosis, and treatment, and ultimately translate to a better outcome of patients with CVT. We present an international research agenda, in which the most important research questions in the field of CVT are prioritized. AIMS: This research agenda has three distinct goals: (1) to provide inspiration and focus to research on CVT for the coming years, (2) to reinforce international collaboration, and (3) to facilitate the acquisition of research funding. SUMMARY OF REVIEW: This international research agenda is the result of a research summit organized by the International Cerebral Venous Thrombosis Consortium in Amsterdam, the Netherlands, in June 2023. The summit brought together 45 participants from 15 countries including clinical researchers from various disciplines, patients who previously suffered from CVT, and delegates from industry and non-profit funding organizations. The research agenda is categorized into six pre-specified themes: (1) epidemiology and clinical features, (2) life after CVT, (3) neuroimaging and diagnosis, (4) pathophysiology, (5) medical treatment, and (6) endovascular treatment. For each theme, we present two to four research questions, followed by a brief substantiation per question. The research questions were prioritized by the participants of the summit through consensus discussion. CONCLUSIONS: This international research agenda provides an overview of the most burning research questions on CVT. Answering these questions will advance our understanding and management of CVT, which will ultimately lead to improved outcomes for CVT patients worldwide.
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Trombosis Intracraneal , Trombosis de la Vena , Humanos , Trombosis Intracraneal/epidemiología , Trombosis Intracraneal/terapia , Trombosis de la Vena/epidemiología , Trombosis de la Vena/terapia , Trombosis de la Vena/diagnóstico , Trombosis de la Vena/prevención & control , Investigación Biomédica , Cooperación InternacionalRESUMEN
Occult atrial fibrillation (AF) is a common cause of cryptogenic stroke. This study aimed to investigate the utility of surrogate markers within the clot (clot markers), in combination with serum biomarkers, to identify AF-associated clots in patients who underwent mechanical thrombectomy. Each retrieved thrombus was analyzed to identify fibrin, red blood cells, platelets - CD61 staining (PLT) and T-CD4 lymphocyte/macrophage/monocyte (CD4) profile. Serum biomarkers such as D-dimer, lipoprotein (A), and brain natriuretic peptide (BNP) were also assessed in the acute phase of the stroke. Patients with stroke-related AF and large artery atherosclerosis (LAA) stroke were compared by matched case-control design to identify markers associated with AF clot profile. The predictive abilities of clot markers and serum biomarkers to detect AF clot were tested in patients with cryptogenic stroke. In patients with AF clot, the PLT percentage was higher (66.64% vs. 55.43%, OR = 1.03); CD4 percentage was lower (3.84% vs. 7.95%, OR = 0.95); and BNP marker was higher (2114 pg/ml vs. 276 pg/ml, OR = 1.04) compared to LAA clot. PLT was independently associated to AF-clot (OR, 1.04) but demonstrated moderate ability to identify AF-clot cases (C-test 0.668, p = 0.018). The combination of PLT with BNP significantly improved AF-clot prediction (C-test 0.847, p < 0.001). The clot composition of patients with cryptogenic stroke and AF detection showed four-fold higher PLT and BNP pattern of risk than patients with cryptogenic stroke without AF detection (38.5% vs. 8.7%) (OR = 1.40). Integrating intra-thrombus platelet with serum BNP offers a promising approach for detecting AF-associated clots in patients with cryptogenic stroke.
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Introduction: Current guidelines recommend that patients with cerebral venous thrombosis (CVT) should be treated with vitamin K antagonists (VKAs) for 3-12 months. Direct oral anticoagulants (DOACs), however, are increasingly used in clinical practice. An exploratory randomized controlled trial including 120 patients with CVT suggested that the efficacy and safety profile of dabigatran (a DOAC) is similar to VKAs for the treatment of CVT, but large-scale prospective studies from a real-world setting are lacking. Methods: DOAC-CVT is an international, prospective, observational cohort study comparing DOACs to VKAs for the prevention of recurrent venous thrombotic events after acute CVT. Patients are eligible if they are 18 years or older, have a radiologically confirmed CVT, and have started oral anticoagulant treatment (DOAC or VKA) within 30 days of CVT diagnosis. Patients with an absolute contra-indication for DOACs, such as pregnancy or severe renal insufficiency, are excluded from the study. We aim to recruit at least 500 patients within a three-year recruitment period. The primary endpoint is a composite of recurrent venous thrombosis and major bleeding at 6 months of follow-up. We will calculate an adjusted odds ratio for the primary endpoint using propensity score inverse probability treatment weighting. Discussion: DOAC-CVT will provide real-world data on the comparative efficacy and safety of DOACs versus VKAs for the treatment of CVT. Clinical trial registration: ClinicalTrials.gov, NCT04660747.
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Importance: ApTOLL is a TLR4 antagonist with proven preclinical neuroprotective effect and a safe profile in healthy volunteers. Objective: To assess the safety and efficacy of ApTOLL in combination with endovascular treatment (EVT) for patients with ischemic stroke. Design, Setting, and Participants: This phase 1b/2a, double-blind, randomized, placebo-controlled study was conducted at 15 sites in Spain and France from 2020 to 2022. Participants included patients aged 18 to 90 years who had ischemic stroke due to large vessel occlusion and were seen within 6 hours after stroke onset; other criteria were an Alberta Stroke Program Early CT Score of 6 to 10, estimated infarct core volume on baseline computed tomography perfusion of 5 to 70 mL, and the intention to undergo EVT. During the study period, 4174 patients underwent EVT. Interventions: In phase 1b, 0.025, 0.05, 0.1, or 0.2 mg/kg of ApTOLL or placebo; in phase 2a, 0.05 or 0.2 mg/kg of ApTOLL or placebo; and in both phases, treatment with EVT and intravenous thrombolysis if indicated. Main Outcomes and Measures: The primary end point was the safety of ApTOLL based on death, symptomatic intracranial hemorrhage (sICH), malignant stroke, and recurrent stroke. Secondary efficacy end points included final infarct volume (via MRI at 72 hours), NIHSS score at 72 hours, and disability at 90 days (modified Rankin Scale [mRS] score). Results: In phase Ib, 32 patients were allocated evenly to the 4 dose groups. After phase 1b was completed with no safety concerns, 2 doses were selected for phase 2a; these 119 patients were randomized to receive ApTOLL, 0.05 mg/kg (n = 36); ApTOLL, 0.2 mg/kg (n = 36), or placebo (n = 47) in a 1:1:â2 ratio. The pooled population of 139 patients had a mean (SD) age of 70 (12) years, 81 patients (58%) were male, and 58 (42%) were female. The primary end point occurred in 16 of 55 patients (29%) receiving placebo (10 deaths [18.2%], 4 sICH [7.3%], 4 malignant strokes [7.3%], and 2 recurrent strokes [3.6%]); in 15 of 42 patients (36%) receiving ApTOLL, 0.05 mg/kg (11 deaths [26.2%], 3 sICH [7.2%], 2 malignant strokes [4.8%], and 2 recurrent strokes [4.8%]); and in 6 of 42 patients (14%) receiving ApTOLL, 0.2 mg/kg (2 deaths [4.8%], 2 sICH [4.8%], and 3 recurrent strokes [7.1%]). ApTOLL, 0.2 mg/kg, was associated with lower NIHSS score at 72 hours (mean difference log-transformed vs placebo, -45%; 95% CI, -67% to -10%), smaller final infarct volume (mean difference log-transformed vs placebo, -42%; 95% CI, -66% to 1%), and lower degrees of disability at 90 days (common odds ratio for a better outcome vs placebo, 2.44; 95% CI, 1.76 to 5.00). Conclusions and Relevance: In acute ischemic stroke, 0.2 mg/kg of ApTOLL administered within 6 hours of onset in combination with EVT was safe and associated with a potential meaningful clinical effect, reducing mortality and disability at 90 days compared with placebo. These preliminary findings await confirmation from larger pivotal trials. Trial Registration: ClinicalTrials.gov Identifier: NCT04734548.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/cirugía , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/complicaciones , Resultado del Tratamiento , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Infarto Cerebral/complicaciones , Hemorragias Intracraneales/etiología , Trombectomía/métodos , Procedimientos Endovasculares/métodosRESUMEN
We aim to identify a profile of intracranial thrombus resistant to recanalization by mechanical thrombectomy (MT) in acute stroke treatment. The first extracted clot of each MT was analyzed by flow cytometry obtaining the composition of the main leukocyte populations: granulocytes, monocytes, and lymphocytes. Demographics, reperfusion treatment, and grade of recanalization were registered. MT failure (MTF) was defined as final thrombolysis in cerebral infarction score IIa or lower and/or need of permanent intracranial stenting as a rescue therapy. To explore the relationship between stiffness of intracranial clots and cellular composition, unconfined compression tests were performed in other cohorts of cases. Thrombi obtained in 225 patients were analyzed. MTF were observed in 30 cases (13%). MTF was associated with atherosclerosis etiology (33.3% vs. 15.9%; p = 0.021) and higher number of passes (3 vs. 2; p < 0.001). Clot analysis of MTF showed higher percentage of granulocytes [82.46 vs. 68.90% p < 0.001] and lower percentage of monocytes [9.18% vs.17.34%, p < 0.001] in comparison to successful MT cases. The proportion of clot granulocytes (aOR 1.07; 95% CI 1.01-1.14) remained an independent marker of MTF. Among thirty-eight clots mechanically tested, there was a positive correlation between granulocyte proportion and thrombi stiffness (Pearson's r = 0.35, p = 0.032), with a median clot stiffness of 30.2 (IQR, 18.9-42.7) kPa. Granulocytes-rich thrombi are harder to capture by mechanical thrombectomy due to increased stiffness, so a proportion of intracranial granulocytes might be useful to guide personalized endovascular procedures in acute stroke treatment.
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Isquemia Encefálica , Trastornos Cerebrovasculares , Accidente Cerebrovascular , Humanos , Trombectomía/métodos , Resultado del Tratamiento , Accidente Cerebrovascular/cirugía , Accidente Cerebrovascular/complicaciones , Granulocitos , Isquemia Encefálica/terapiaRESUMEN
BACKGROUND: In proximal occlusions, the effect of reperfusion therapies may differ between slow or fast progressors. We investigated the effect of intravenous thrombolysis (IVT) (with alteplase) plus mechanical thrombectomy (MT) versus thrombectomy alone among slow versus fast stroke progressors. METHODS: The SWIFT-DIRECT trial data were analyzed: 408 patients randomized to IVT+MT or MT alone. Infarct growth speed was defined by the number of points of decay in the initial Alberta Stroke Program Early CT Score (ASPECTS) divided by the onset-to-imaging time. The primary endpoint was 3-month functional independence (modified Rankin scale 0-2). In the primary analysis, the study population was dichotomized into slow and fast progressors using median infarct growth velocity. Secondary analysis was also conducted using quartiles of ASPECTS decay. RESULTS: We included 376 patients: 191 IVT+MT, 185 MT alone; median age 73 years (IQR 65-81); median initial National Institutes of Health Stroke Scale (NIHSS) 17 (IQR 13-20). The median infarct growth velocity was 1.2 points/hour. Overall, we did not observe a significant interaction between the infarct growth speed and the allocation to either randomization group on the odds of favourable outcome (P=0.68). In the IVT+MT group, odds of any intracranial hemorrhage (ICH) were significantly lower in slow progressors (22.8% vs 36.4%; OR 0.52, 95% CI 0.27 to 0.98) and higher among fast progressors (49.4% vs 26.8%; OR 2.62, 95% CI 1.42 to 4.82) (P value for interaction <0.001). Similar results were observed in secondary analyses. CONCLUSION: In this SWIFT-DIRECT subanalysis, we did not find evidence for a significant interaction of the velocity of infarct growth on the odds of favourable outcome according to treatment by MT alone or combined IVT+MT. However, prior IVT was associated with significantly reduced occurrence of any ICH among slow progressors whereas this was increased in fast progressors.
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Isquemia Encefálica , Trombolisis Mecánica , Accidente Cerebrovascular , Humanos , Anciano , Resultado del Tratamiento , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/cirugía , Trombectomía/métodos , Terapia Trombolítica/métodos , Hemorragias Intracraneales/complicaciones , Infarto/complicaciones , Infarto/tratamiento farmacológico , Isquemia Encefálica/terapia , Fibrinolíticos/uso terapéutico , Trombolisis Mecánica/métodosRESUMEN
BACKGROUND: Migraine is one of the most prevalent and disabling medical diseases in the world. The periaqueductal gray matter and the red nucleus play an important role in its pathogenesis. Our aim was to evaluate the echogenicity of the periaqueductal gray matter and the red nucleus in patients with migraine, by means of transcranial ultrasound. METHODS: In this cross-sectional study, a group of patients with migraine (according to the International Classification of Headache Disorders) and a group of control subjects with comparable age-and-sex distribution were prospectively included. We evaluated the area and echogenicity of the periaqueductal gray matter and the red nucleus by means of transcranial ultrasound, both bedside and posteriorly analyzed with the medical image viewer Horos. RESULTS: We included 115 subjects: 65 patients with migraine (39 of them with chronic migraine and 26 with episodic migraine), and 50 controls. Median disease duration in patients with chronic migraine was 29 (IQR: 19; 40) years, with a median of 18 (IQR: 14; 27) days of migraine per month. The area of the periaqueductal gray matter was larger in patients with chronic migraine compared to episodic migraine and controls (0.15[95%CI 0.12;0.22]cm2; 0.11[95%CI 0.10;0.14]cm2 and 0.12[95%CI 0.09;0.15]cm2, respectively; p = 0.043). Chronic migraine patients showed an intensity of the periaqueductal gray matter echogenicity lower than controls (90.57[95%CI 70.87;117.26] vs 109.56[95%CI 83.30;122.64]; p = 0.035). The coefficient of variation of periaqueductal gray matter echogenicity was the highest in chronic migraine patients (p = 0.009). No differences were observed regarding the area or intensity of red nucleus echogenicity among groups. CONCLUSION: Patients with chronic migraine showed a larger area of echogenicity of periaqueductal gray matter, a lower intensity of its echogenicity and a higher heterogenicity within this brainstem structure compared to patients with episodic migraine and controls. The echogenicity of the periaqueductal gray matter should be further investigated as a biomarker of migraine chronification.
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Imagen por Resonancia Magnética , Trastornos Migrañosos , Humanos , Estudios de Casos y Controles , Imagen por Resonancia Magnética/métodos , Sustancia Gris Periacueductal/diagnóstico por imagen , Estudios Transversales , Trastornos Migrañosos/diagnóstico por imagen , Trastornos Migrañosos/patología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patologíaRESUMEN
In the reperfusion era, a new paradigm of treating patients with endovascular treatment (EVT) and neuroprotective drugs is emerging as a promising therapeutic option for patients with acute ischemic stroke (AIS). In this context, ApTOLL, a Toll-like receptor 4 (TLR4) antagonist with proven neuroprotective effect in preclinical models of stroke and a very good pharmacokinetic and safety profile in healthy volunteers, is a promising first-in-class aptamer with the potential to address this huge unmet need. This protocol establishes the clinical trial procedures to conduct a Phase Ib/IIa clinical study (APRIL) to assess ApTOLL tolerability, safety, pharmacokinetics, and biological effect in patients with AIS who are eligible for EVT. This will be a multicenter, double-blind, randomized, placebo-controlled, Phase Ib/IIa clinical study to evaluate the administration of ApTOLL together with EVT in patients with AIS. The study population will be composed of men and non-pregnant women with confirmed AIS with a <6h window from symptoms onset to ApTOLL/placebo administration. The trial is currently being conducted and is divided into two parts: Phase Ib and Phase IIa. In Phase Ib, 32 patients will be allocated to four dose ascending levels to select, based on safety criteria, the best two doses to be administered in the following Phase IIa in which 119 patients will be randomized to three arms of treatment (dose A, dose B, and placebo). Identification of the trial: EudraCT: 2020-002059-38 and ClinicalTrials.gov Identifier: NCT04734548 https://clinicaltrials.gov/ct2/show/NCT04734548?term=ApTOLL&cond=Stroke&draw=2&rank=1.
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The need for advances in the management/treatment options for ischemic stroke patients requires that upcoming preclinical research uses animals with more human-like brain characteristics. The porcine brain is considered appropriate, although the presence of the rete mirabile (RM) prevents direct catheterization of the intracranial arteries to produce focal cerebral ischemia. To develop a reproducible minimally invasive porcine stroke model, a guide catheter and guide wire were introduced through the femoral artery until reaching the left RM. Using the pressure cooker technique, Squid-12 embolization material was deposited to fill, overflow, and occlude the left RM, the left internal carotid artery, and left circle of Willis wing up to the origins of the middle cerebral arteries (MCAs), mimicking the occlusion produced in the filament model in rodents. Longitudinal multimodal cerebral MRI was conducted to assess the brain damage and cerebral blood supply. The technique we describe here occluded up to the origins of the MCAs in 7 of 8 swine, inducing early damage 90 minutes after occlusion that later evolved to a large cerebral infarction and producing no mortality during the intervention. This minimally invasive ischemic stroke model in swine produced reproducible infarcts and shows translational features common to human stroke.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Animales , Porcinos , Isquemia Encefálica/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , ArteriasRESUMEN
BACKGROUND AND PURPOSE: The prognostic significance of postcontrast enhancement of intracranial atheromatous plaque is uncertain. Prospective, long-term follow-up studies in Caucasians, using a multicenter design, are lacking. We aimed to evaluate whether this radiological sign predicts long-term new stroke in symptomatic and asymptomatic intracranial atherosclerotic disease (ICAD) patients. METHODS: This was a prospective, observational, longitudinal, multicenter study. We included a symptomatic and an asymptomatic cohort of ICAD patients that underwent 3T MRI including high-resolution sequences focused on the atheromatous plaque. We evaluated grade of stenosis, plaque characteristics, and gadolinium enhancement ratio (postcontrast plaque signal/postcontrast corpus callosum signal). The occurrence of new events was evaluated at 3, 6, 9, and 12 months and annually thereafter. The association between plaque characteristics and new stroke was studied using Cox multiple regression survival analysis and Kaplan-Meier curves. RESULTS: Forty-eight symptomatic and 13 asymptomatic patients were included. During 56.3 ± 16.9 months, 11 patients (18%) suffered a new event (seven ischemic, two hemorrhagic, and two transient ischemic attacks). A receiver operating characteristic curve identified an enhancement ratio of >1.77 to predict a new event. In a multivariable Cox regression, postcontrast enhancement ratio >1.77 (hazard ratio [HR]= 3.632; 95% confidence interval [CI], 1.082-12.101) and cerebral microbleeds (HR = 5.244; 95% CI, 1.476-18.629) were independent predictors of future strokes. Patients with a plaque enhancement ratio >1.77 had a lower survival free of events (p < .05). CONCLUSIONS: High intracranial postcontrast enhancement is a long-term predictor of new stroke in ICAD patients. Further studies are needed to elucidate whether postcontrast enhancement reflects inflammatory activity of intracranial atheromatous plaque.
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Arteriosclerosis Intracraneal , Placa Aterosclerótica , Accidente Cerebrovascular , Humanos , Estudios Prospectivos , Medios de Contraste , Estudios Longitudinales , Gadolinio , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: The first pass effect (FPE) is an independent predictor of functional independence in patients with large vessel occlusion in anterior circulation ischemic strokes. However, whether it predicts outcome in posterior circulation large vessel occlusion (PC-LVO) is uncertain. We aimed to study the frequency, characteristics, and predictors of FPE and its association with clinical outcomes in PC-LVO. METHOD: We performed an analysis from the prospective CICAT Registry. All patients with PC-LVO who underwent endovascular therapy between January 2016 and January 2020 were included. A centrally assessed clinical follow-up was performed at 3 months by blinded investigators. FPE was defined as the achievement of modified Thrombolysis In Cerebral Infarction 3 in a single pass of the endovascular thrombectomy device, and multi-pass effect (MPE) if it was achieved in more than one pass. A multivariable analysis was performed to identify whether FPE is an independent predictor of functional independence defined as a modified Rankin Score of 0-2. RESULTS: We analyzed data from 265 patients in who FPE was achieved in 105 (39.6%). Patients with FPE were more likely to achieve functional independence compared to the non-FPE group (52.4% vs 25.1%, p < .001) and the MPE group (52.4% vs 26.7%, p < .001). FPE was independently associated with functional independence (adjusted odds ratio (aOR): 2.10, 95% confidence interval (CI) 1.01-4.37) but MPE was not (aOR: 0.92, 95% CI 0.40-2.13). Independent predictors of FPE were the use of direct aspiration, embolic mechanism of stroke, and the absence of general anesthesia (GA) use. CONCLUSIONS: FPE is an independent predictor of functional independence in PC-LVO and was associated with a significantly better outcome than MPE.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/etiología , Estudios Prospectivos , Resultado del Tratamiento , Trombectomía , Sistema de Registros , Estudios Retrospectivos , Isquemia Encefálica/terapia , Isquemia Encefálica/etiología , Procedimientos Endovasculares/efectos adversosRESUMEN
BACKGROUND: We studied the evolution over time of diffusion weighted imaging (DWI) lesion volume and the factors involved on early and late infarct growth (EIG and LIG) in stroke patients undergoing endovascular treatment (EVT) according to the final revascularization grade. METHODS: This is a prospective cohort of patients with anterior large artery occlusion undergoing EVT arriving at 1 comprehensive stroke center. Magnetic resonance imaging was performed on arrival (pre-EVT), <2 hours after EVT (post-EVT), and on day 5. DWI lesions and perfusion maps were evaluated. Arterial revascularization was assessed according to the modified Thrombolysis in Cerebral Infarction (mTICI) grades. We recorded National Institutes of Health Stroke Scale at arrival and at day 7. EIG was defined as (DWI volume post-EVT-DWI volume pre-EVT), and LIG was defined as (DWI volume at 5d-DWI volume post-EVT). Factors involved in EIG and LIG were tested via multivariable lineal models. RESULTS: We included 98 patients (mean age 70, median National Institutes of Health Stroke Scale score 17, final mTICI≥2b 86%). Median EIG and LIG were 48 and 63.3 mL in patients with final mTICI<2b, and 3.6 and 3.9 cc in patients with final mTICI≥2b. Both EIG and LIG were associated with higher National Institutes of Health Stroke Scale at day 7 (ρ=0.667; P<0.01 and ρ=0.614; P<0.01, respectively). In patients with final mTICI≥2b, each 10% increase in the volume of DWI pre-EVT and each extra pass leaded to growths of 9% (95% CI, 7%-10%) and 14% (95% CI, 2%-28%) in the DWI volume post-EVT, respectively. Furthermore, each 10% increase in the volume of DWI post-EVT, each extra pass, and each 10 mL increase in TMax6s post-EVT were associated with growths of 8% (95% CI, 6%-9%), 9% (95% CI, 0%-19%), and 12% (95% CI, 5%-20%) in the volume of DWI post-EVT, respectively. CONCLUSIONS: Infarct grows during and after EVT, especially in nonrecanalizers but also to a lesser extent in recanalizers. In recanalizers, number of passes and DWI volume influence EIG, while number of passes, DWI, and hypoperfused volume after the procedure determine LIG.
Asunto(s)
Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular , Humanos , Anciano , Estudios Prospectivos , Resultado del Tratamiento , Accidente Cerebrovascular/terapia , Infarto Cerebral/complicaciones , Imagen por Resonancia Magnética , Trombectomía/métodos , Procedimientos Endovasculares/métodos , Isquemia Encefálica/complicaciones , Estudios RetrospectivosRESUMEN
BACKGROUND AND PURPOSE: Hypoechogenicity of the raphe nuclei (hR) has been related to major depression. Comorbidity between migraine and depression is bidirectional postulating a common mechanism of serotonergic dysfunction. We aimed to investigate the association between migraine and hR and its role as biomarker of migraine-associated depression and disease severity. METHODS: This is a single-center cross-sectional descriptive study. We included consecutive patients with episodic (EM) and chronic migraine (CM). We collected their comorbidities, analgesic consumption, hospital anxiety and depression scale (HADS), disability, and impact on quality of life associated with migraine. We also included a group of control subjects, matched for age and sex with the patients. In both groups, hR was assessed by means of transcranial sonography. We performed a meta-analysis of the studies investigating the association between migraine and hR. RESULTS: A total of 107 subjects were included (57 cases and 50 controls). hR rate was lower in controls than in migraine patients (22.2% vs. 42.9%, p = .02) with a progressive increase in EM and CM groups respect to the control group (33.3% and 50% vs. 22.2%, respectively; p = .03). Among patients, hR was not associated with depression, higher HADS score, greater migraine-related disability, or higher consumption of analgesic medication. The meta-analysis showed a significant association between migraine and hR (odds ratio = 2.16; 95% confidence interval: 1.42-3.29). CONCLUSION: hR is more prevalent in migraine patients than in controls and, in our population, its prevalence increases in a stepwise manner in patients with EM and CM. These findings support the role of raphe nuclei in migraine pathophysiology.