Wallenberg's syndrome as the presenting symptom of a cavernous angioma

Introducción: los angiomas cavernosos representan el 5-13% del total de malformaciones vasculares. En el 75% de los casos se encuentran en la fosa posterior, y hasta en el 30%, asociado a un drenaje venoso anómalo. La principal complicación son las hemorragias; es excepcional la presencia de focalidad neurológica sin evidencia radiológica de sangrado. Caso clínico: presentamos un caso de un varón de 54 años con factores de riesgo cardiovascular, que muestra un cuadro progresivo en 72 horas de duración de afectación de los pares craneales bajos izquierdos, déficit sensitivo y alteración de la coordinación compatible con un síndrome de Wallenberg. Con la tomografía axial computarizada craneal en dos ocasiones normal, se realizó la orientación diagnóstica de ictus vertebrobasilar en progresión. Cinco días después, la resonancia magnética (RM) demostró la presencia de un angioma venoso y un drenaje venoso anómalo asociado. Conclusión: los angiomas cavernosos presentan un equilibrio dinámico de sangrado y trombosis de intracavernoma, con un flujo venoso muy lento. Una rotura en este equilibrio supone un aumento de la presión de intracavernoma y la afectación del tejido circundante, sin expresión radiológica de sangrado. La RM ayuda en estos casos a diferenciar una malformación vascular de flujo lento de un cuadro ictal isquémico de origen arterial

Circulating AQP4 Levels in Patients with Cerebral Amyloid Angiopathy-Associated Intracerebral Hemorrhage

Cerebral amyloid angiopathy (CAA) is a major cause of lobar intracerebral hemorrhage (ICH) in elderly patients. Growing evidence suggests a potential role of aquaporin 4 (AQP4) in amyloid-beta-associated diseases, including CAA pathology. Our aim was to investigate the circulating levels of AQP4 in a cohort of patients who had suffered a lobar ICH with a clinical diagnosis of CAA. AQP4 levels were analyzed in the serum of 60 CAA-related ICH patients and 19 non-stroke subjects by enzyme-linked immunosorbent assay (ELISA). The CAA-ICH cohort was divided according to the time point of the functional outcome evaluation: mid-term (12 +/- 18.6 months) and long-term (38.5 +/- 32.9 months) after the last ICH. Although no differences were found in AQP4 serum levels between cases and controls, lower levels were found in CAA patients presenting specific hemorrhagic features such as >= 2 lobar ICHs and >= 5 lobar microbleeds detected by magnetic resonance imaging (MRI). In addition, CAA-related ICH patients who presented a long-term good functional outcome had higher circulating AQP4 levels than subjects with a poor outcome or controls. Our data suggest that AQP4 could potentially predict a long-term functional outcome and may play a protective role after a lobar ICH

Comparison of Plasma Lipoprotein Composition and Function in Cerebral Amyloid Angiopathy and Alzheimer’s Disease

Cerebral amyloid angiopathy (CAA) refers to beta-amyloid (Aβ) deposition in brain vessels and is clinically the main cause of lobar intracerebral hemorrhage (ICH). Aβ can also accumulate in brain parenchyma forming neuritic plaques in Alzheimer's disease (AD). Our study aimed to determine whether the peripheral lipid profile and lipoprotein composition are associated with cerebral beta-amyloidosis pathology and may reflect biological differences in AD and CAA. For this purpose, lipid and apolipoproteins levels were analyzed in plasma from 51 ICH-CAA patients (collected during the chronic phase of the disease), 60 AD patients, and 60 control subjects. Lipoproteins (VLDL, LDL, and HDL) were isolated and their composition and pro/antioxidant ability were determined. We observed that alterations in the lipid profile and lipoprotein composition were remarkable in the ICH-CAA group compared to control subjects, whereas the AD group presented no specific alterations compared with controls. ICH-CAA patients presented an atheroprotective profile, which consisted of lower total and LDL cholesterol levels. Plasma from chronic ICH-CAA patients also showed a redistribution of ApoC-III from HDL to VLDL and a higher ApoE/ApoC-III ratio in HDL. Whether these alterations reflect a protective response or have a causative effect on the pathology requires further investigation

Thrombectomy within 8 hours after symptom onset in ischemic stroke

BACKGROUND: We aimed to assess the safety and efficacy of thrombectomy for the treatment of stroke in a trial embedded within a population-based stroke reperfusion registry. METHODS: During a 2-year period at four centers in Catalonia, Spain, we randomly assigned 206 patients who could be treated within 8 hours after the onset of symptoms of acute ischemic stroke to receive either medical therapy (including intravenous alteplase when eligible) and endovascular therapy with the Solitaire stent retriever (thrombectomy group) or medical therapy alone (control group). All patients had confirmed proximal anterior circulation occlusion and the absence of a large infarct on neuroimaging. In all study patients, the use of alteplase either did not achieve revascularization or was contraindicated. The primary outcome was the severity of global disability at 90 days, as measured on the modified Rankin scale (ranging from 0 [no symptoms] to 6 [death]). Although the maximum planned sample size was 690, enrollment was halted early because of loss of equipoise after positive results for thrombectomy were reported from other similar trials. RESULTS Thrombectomy reduced the severity of disability over the range of the modified Rankin scale (adjusted odds ratio for improvement of 1 point, 1.7; 95% confidence interval [CI], 1.05 to 2.8) and led to higher rates of functional independence (a score of 0 to 2) at 90 days (43.7% vs. 28.2%; adjusted odds ratio, 2.1; 95% CI, 1.1 to 4.0). At 90 days, the rates of symptomatic intracranial hemorrhage were 1.9% in both the thrombectomy group and the control group (P = 1.00), and rates of death were 18.4% and 15.5%, respectively (P = 0.60). Registry data indicated that only eight patients who met the eligibility criteria were treated outside the trial at participating hospitals. CONCLUSIONS: Among patients with anterior circulation stroke who could be treated within 8 hours after symptom onset, stent retriever thrombectomy reduced the severity of post-stroke disability and increased the rate of functional independence

Safety and efficacy of ApTOLL in patients with ischemic stroke undergoing endovascular treatment: a phase 1/2 randomized clinical trial

Clinical trial[Abstract] 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:√2 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.This study was sponsored by aptaTargets, Madrid, Spain, and cofunded by grants from the Spanish Ministry of Science, Innovation and Universities (RTC-2017-6651-1 and RTC-2019-006795-1).España. Ministerio de Ciencia, Innovación e Universidades; RTC-2017-6651-1España. Ministeriod e Ciencia, Innovación e Universidades; RTC-2019-006795-

Left atrial appendage occlusion plus oral anticoagulation in stroke patients despite ongoing anticoagulation: rationale and design of the ADD-LAAO clinical trial

[spa] Introduction and objectives: The prevalence of atrial fibrillation and the number of patients experiencing ischemic strokes despite oral anticoagulation (OAC) are both on the rise, which presents a significant challenge due to the absence of clear and uniform treatment recommendations for these patients. To date, there is no formal combination merging into a high anticoagulant efficacy profile while keeping a low bleeding risk. Transcatheter left atrial appendage occlusion (LAAO) in combination with OAC might provide a balance between safety and efficacy. The objective of this study is to evaluate whether, in ischemic stroke patients, despite anticoagulation, the combination of LAAO plus long-term anticoagulation-direct oral anticoagulants or vitamin K antagonist when indicated-is associated with a lower rate of recurrent cardioembolic events at 12 months vs the optimal medical therapy recommended by the neurologist. Methods: A total of 380 patients with ischemic stroke despite OAC will be included. Patients will be randomized on a 1:1 ratio to receive the optimal medical therapy (control) or the combination of LAAO plus OAC or OAC. The primary endpoint of the study will be the occurrence of a cardioembolic event-ischemic stroke or arterial peripheral embolism-within the first 12 months after inclusion. Conclusions: This study is one of the first randomized clinical trials to compare the LAAO plus OAC combination and optimal medical therapy in patients who have experienced ischemic strokes despite being on OAC. If results confirm the superiority of LAAO plus OAC, it could lead to a paradigm shift in treatment guidelines for these patients.[eng] Introduction and objectives: The prevalence of atrial fibrillation and the number of patients experiencing ischemic strokes despite oral anticoagulation (OAC) are both on the rise, which presents a significant challenge due to the absence of clear and uniform treatment recommendations for these patients. To date, there is no formal combination merging into a high anticoagulant efficacy profile while keeping a low bleeding risk. Transcatheter left atrial appendage occlusion (LAAO) in combination with OAC might provide a balance between safety and efficacy. The objective of this study is to evaluate whether, in ischemic stroke patients, despite anticoagulation, the combination of LAAO plus long-term anticoagulation—direct oral anticoagulants or vitamin K antagonist when indicated—is associated with a lower rate of recurrent cardioembolic events at 12 months vs the optimal medical therapy recommended by the neurologist. Methods: A total of 380 patients with ischemic stroke despite OAC will be included. Patients will be randomized on a 1:1 ratio to receive the optimal medical therapy (control) or the combination of LAAO plus OAC or OAC. The primary endpoint of the study will be the occurrence of a cardioembolic event—ischemic stroke or arterial peripheral embolism—within the first 12 months after inclusion. Conclusions: This study is one of the first randomized clinical trials to compare the LAAO plus OAC combination and optimal medical therapy in patients who have experienced ischemic strokes despite being on OAC. If results confirm the superiority of LAAO plus OAC, it could lead to a paradigm shift in treatment guidelines for these patients

Association of Endovascular Thrombectomy vs Medical Management With Functional and Safety Outcomes in Patients Treated Beyond 24 Hours of Last Known Well: The SELECT Late Study

IMPORTANCE: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well. OBJECTIVE: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well. DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or medical management beyond 24 hours of last known well. INTERVENTIONS: Endovascular thrombectomy or medical management (control). MAIN OUTCOMES AND MEASURES: Primary outcome was functional independence (modified Rankin Scale score 0-2). Mortality and symptomatic intracranial hemorrhage (sICH) were safety outcomes. Propensity score (PS)-weighted multivariable logistic regression analyses were adjusted for prespecified clinical characteristics, perfusion parameters, and/or Alberta Stroke Program Early CT Score (ASPECTS) and were repeated in subsequent 1:1 PS-matched cohorts. RESULTS: Of 301 patients (median [IQR] age, 69 years [59-81]; 149 female), 185 patients (61%) received EVT and 116 (39%) received medical management. In adjusted analyses, EVT was associated with better functional independence (38% vs control, 10%; inverse probability treatment weighting adjusted odds ratio [IPTW aOR], 4.56; 95% CI, 2.28-9.09; P \u3c .001) despite increased odds of sICH (10.1% for EVT vs 1.7% for control; IPTW aOR, 10.65; 95% CI, 2.19-51.69; P = .003). This association persisted after PS-based matching on (1) clinical characteristics and ASPECTS (EVT, 35%, vs control, 19%; aOR, 3.14; 95% CI, 1.02-9.72; P = .047); (2) clinical characteristics and perfusion parameters (EVT, 35%, vs control, 17%; aOR, 4.17; 95% CI, 1.15-15.17; P = .03); and (3) clinical characteristics, ASPECTS, and perfusion parameters (EVT, 45%, vs control, 21%; aOR, 4.39; 95% CI, 1.04-18.53; P = .04). Patients receiving EVT had lower odds of mortality (26%) compared with those in the control group (41%; IPTW aOR, 0.49; 95% CI, 0.27-0.89; P = .02). CONCLUSIONS AND RELEVANCE: In this study of treatment beyond 24 hours of last known well, EVT was associated with higher odds of functional independence compared with medical management, with consistent results obtained in PS-matched subpopulations and patients with presence of mismatch, despite increased odds of sICH. Our findings support EVT feasibility in selected patients beyond 24 hours. Prospective studies are warranted for confirmation

Association of Endovascular Thrombectomy vs Medical Management With Functional and Safety Outcomes in Patients Treated Beyond 24 Hours of Last Known Well: The SELECT Late Study

IMPORTANCE: The role of endovascular thrombectomy is uncertain for patients presenting beyond 24 hours of the time they were last known well. OBJECTIVE: To evaluate functional and safety outcomes for endovascular thrombectomy (EVT) vs medical management in patients with large-vessel occlusion beyond 24 hours of last known well. DESIGN, SETTING, AND PARTICIPANTS: This retrospective observational cohort study enrolled patients between July 2012 and December 2021 at 17 centers across the United States, Spain, Australia, and New Zealand. Eligible patients had occlusions in the internal carotid artery or middle cerebral artery (M1 or M2 segment) and were treated with EVT or medical management beyond 24 hours of last known well. INTERVENTIONS: Endovascular thrombectomy or medical management (control). MAIN OUTCOMES AND MEASURES: Primary outcome was functional independence (modified Rankin Scale score 0-2). Mortality and symptomatic intracranial hemorrhage (sICH) were safety outcomes. Propensity score (PS)-weighted multivariable logistic regression analyses were adjusted for prespecified clinical characteristics, perfusion parameters, and/or Alberta Stroke Program Early CT Score (ASPECTS) and were repeated in subsequent 1:1 PS-matched cohorts. RESULTS: Of 301 patients (median [IQR] age, 69 years [59-81]; 149 female), 185 patients (61%) received EVT and 116 (39%) received medical management. In adjusted analyses, EVT was associated with better functional independence (38% vs control, 10%; inverse probability treatment weighting adjusted odds ratio [IPTW aOR], 4.56; 95% CI, 2.28-9.09; P \u3c .001) despite increased odds of sICH (10.1% for EVT vs 1.7% for control; IPTW aOR, 10.65; 95% CI, 2.19-51.69; P = .003). This association persisted after PS-based matching on (1) clinical characteristics and ASPECTS (EVT, 35%, vs control, 19%; aOR, 3.14; 95% CI, 1.02-9.72; P = .047); (2) clinical characteristics and perfusion parameters (EVT, 35%, vs control, 17%; aOR, 4.17; 95% CI, 1.15-15.17; P = .03); and (3) clinical characteristics, ASPECTS, and perfusion parameters (EVT, 45%, vs control, 21%; aOR, 4.39; 95% CI, 1.04-18.53; P = .04). Patients receiving EVT had lower odds of mortality (26%) compared with those in the control group (41%; IPTW aOR, 0.49; 95% CI, 0.27-0.89; P = .02). CONCLUSIONS AND RELEVANCE: In this study of treatment beyond 24 hours of last known well, EVT was associated with higher odds of functional independence compared with medical management, with consistent results obtained in PS-matched subpopulations and patients with presence of mismatch, despite increased odds of sICH. Our findings support EVT feasibility in selected patients beyond 24 hours. Prospective studies are warranted for confirmation

Wallenberg's syndrome as the presenting symptom of a cavernous angioma

Introducción: los angiomas cavernosos representan el 5-13% del total de malformaciones vasculares. En el 75% de los casos se encuentran en la fosa posterior, y hasta en el 30%, asociado a un drenaje venoso anómalo. La principal complicación son las hemorragias; es excepcional la presencia de focalidad neurológica sin evidencia radiológica de sangrado. Caso clínico: presentamos un caso de un varón de 54 años con factores de riesgo cardiovascular, que muestra un cuadro progresivo en 72 horas de duración de afectación de los pares craneales bajos izquierdos, déficit sensitivo y alteración de la coordinación compatible con un síndrome de Wallenberg. Con la tomografía axial computarizada craneal en dos ocasiones normal, se realizó la orientación diagnóstica de ictus vertebrobasilar en progresión. Cinco días después, la resonancia magnética (RM) demostró la presencia de un angioma venoso y un drenaje venoso anómalo asociado. Conclusión: los angiomas cavernosos presentan un equilibrio dinámico de sangrado y trombosis de intracavernoma, con un flujo venoso muy lento. Una rotura en este equilibrio supone un aumento de la presión de intracavernoma y la afectación del tejido circundante, sin expresión radiológica de sangrado. La RM ayuda en estos casos a diferenciar una malformación vascular de flujo lento de un cuadro ictal isquémico de origen arterial

Cerebral venous thrombosis as the presenting symptom of systemic lupus erythematosus

Introducción: la trombosis venosa cerebral (TVC) es una proceso inhabitual en el lupus eritematosos sistémico. Presentamos una paciente cuya manifestación inicial del lupus fue una TVC. Caso clínico: paciente de 30 años de edad que presenta cefalea y disminución de la agudeza visual; en la exploración destaca papiledema bilateral. La resonancia magnética realizada demuestra la presencia de una trombosis venosa en el seno longitudinal superior y transverso. Las exploraciones complementarias mostraron unos niveles elevados de anticuerpos antinucleares con leucopenia y proteinuria. Los anticuerpos antifosfolípidos fueron negativos. Tras tratamiento anticoagulante, mejoró clínica y radiológicamente. Meses más tarde se realizó biopsia, que demostró una glomerulonefritis difusa grado IV. Conclusión: en el lupus eritematosos sistémico, fenómenos como la TVC pueden ser la forma de manifestación inicial de la enfermedad. La presencia de anticuerpos antifosfolípidos participa de forma parcial en la TVC; deberían considerarse otros fenómenos, como los inflamatorios