Prognostic impact of intracranial arteriosclerosis subtype after endovascular treatment for acute ischaemic stroke.

BACKGROUND AND PURPOSE: The influence of intracranial arteriosclerosis (ICAR) on acute ischaemic stroke (AIS) prognosis is unclear. This study explored its impact, focusing on ICAR subtypes categorized by intracranial carotid artery calcification (ICAC) patterns: intimal or atherosclerotic versus internal elastic lamina calcification or non-atherosclerotic. The aim was to determine their effect on AIS prognosis in patients undergoing endovascular treatment (EVT). METHODS: This prospective cohort study included consecutive AIS patients with anterior circulation large vessel occlusion undergoing EVT. ICAC, the hallmark of ICAR, was assessed using non-contrast computed tomography to quantify volume and establish the predominant ICAR subtype. The primary outcome was long-term functional outcome, measured by the 90-day modified Rankin Scale score. Secondary outcomes included first-pass effect, revascularization degree, symptomatic intracranial haemorrhage and 24-h infarct volume. Multivariate-adjusted linear and logistic regression models were used to assess the association of ICAC volume and subtype with these outcomes. RESULTS: From January 2021 to February 2022, 181 patients were included, of whom 172 (95%) had ICAC. Internal elastic lamina calcification was the predominant subtype in 103 (57%), intimal in 52 (29%) and mixed in 17 (9%). The intimal or atherosclerotic ICAC pattern was linked to poorer functional outcomes (adjusted odds ratio 2.12, 95% confidence interval [CI] 1.10-4.09), decreased first-pass effect probability (adjusted odds ratio 0.42, 95% CI 0.21-0.84) and higher infarct volume (adjusted ß value 22.11, 95% CI 0.55-43.67). CONCLUSIONS: A predominant intimal ICAC subtype, linked to underlying atherosclerosis, correlated with larger infarct volume and poorer 90-day functional outcomes in EVT-treated AIS patients. Intracranial atherosclerosis appears to be a relevant factor hampering clinical benefits post-EVT.

Thrombectomy versus Medical Management in Mild Strokes due to Large Vessel Occlusion: Exploratory Analysis from the EXTEND-IA Trials and a Pooled International Cohort.

OBJECTIVE: This study was undertaken to evaluate functional and safety outcomes for endovascular thrombectomy (EVT) versus medical management (MM) in patients with large vessel occlusion (LVO) and mild neurological deficits, stratified by perfusion imaging mismatch. METHODS: The pooled cohort consisted of patients with National Institutes of Health Stroke Scale (NIHSS) < 6 and internal carotid artery (ICA), M1, or M2 occlusions from the Extending the Time for Thrombolysis in Emergecy Neurological Deficits - Intra-Arterial (EXTEND-IA) Trial,  Tenecteplase vs Alteplase before Endovascular Thrombectomy in Ischemic Stroke (EXTEND-IA TNK) trials Part I/II and prospective data from 15 EVT centers from October 2010 to April 2020. RAPID software estimated ischemic core and mismatch. Patients receiving primary EVT (EVTpri ) were compared to those who received primary MM (MMpri ), including those who deteriorated and received rescue EVT, in overall and propensity score (PS)-matched cohorts. Patients were stratified by target mismatch (mismatch ratio ≥ 1.8 and mismatch volume ≥ 15ml). Primary outcome was functional independence (90-day modified Rankin Scale = 0-2). Secondary outcomes included safety (symptomatic intracerebral hemorrhage [sICH], neurological worsening, and mortality). RESULTS: Of 540 patients, 286 (53%) received EVTpri and demonstrated larger critically hypoperfused tissue (Tmax > 6 seconds) volumes (median [IQR]: 64 [26-96] ml vs MMpri : 40 [14-76] ml, p < 0.001) and higher presentation NIHSS (median [IQR]: 4 [2-5] vs MMpri : 3 [2-4], p < 0.001). Functional independence was similar (EVTpri : 77.4% vs MMpri : 75.6%, adjusted odds ratio [aOR] = 1.29, 95% confidence interval [CI] = 0.82-2.03, p = 0.27). EVT had worse safety regarding sICH (EVTpri : 16.3% vs MMpri : 1.3%, p < 0.001) and neurological worsening (EVTpri : 19.6% vs MMpri : 6.7%, p < 0.001). In 414 subjects (76.7%) with target mismatch, EVT was associated with improved functional independence (EVTpri : 77.4% vs MMpri : 72.7%, aOR = 1.68, 95% CI = 1.01-2.81, p = 0.048), whereas there was a trend toward less favorable outcomes with primary EVT (EVTpri : 77.4% vs MMpri : 83.3%, aOR = 0.39, 95% CI = 0.12-1.34, p = 0.13) without target mismatch (pinteraction  = 0.06). Similar findings were observed in a propensity score-matched subpopulation. INTERPRETATION: Overall, EVT was not associated with improved clinical outcomes in mild strokes due to LVO, and sICH was increased. However, in patients with target mismatch profile, EVT was associated with increased functional independence. Perfusion imaging may be helpful to select mild stroke patients for EVT. ANN NEUROL 2022;92:364-378.

Intensive 90-day textile wearable Holter monitoring: an alternative to detect paroxysmal atrial fibrillation in selected patients with cryptogenic stroke.

We aimed to demonstrate the feasibility of 90-day cardiac monitoring with an external Holter device and to find a target population able to benefit from such a technique. Cryptogenic stroke patients were continuously monitored for 90 days with a textile wearable Holter (TWH). Compliance and quality of the monitoring were assessed by the number of hours of ECG stored per month. Mean predictors of pAF, including age, gender, stroke severity, and atrial size (LAVI), were evaluated. One-year follow-up assessed pAF detection outside per protocol monitoring. Out of 224 patients included in 5 stroke centers, 163 patients (72.76%) fulfilled the criteria for the protocol. Median monitoring time was similar among the three months. Per protocol pAF detection reached 35.37% at 90 days. The age (OR 1.095; 95% CI 1.03-1.14) and the LAVI (OR 1.055; 95% CI 1.01-1.09) independently predicted pAF. The cut-off point of 70 years (AUC 0.68) (95% CI 0.60-0.76) predicted pAF with a sensitivity of 75.8% and specificity of 50.5%. The LAVI cut-off point of 28.5 (AUC 0.67) (95% CI 0.56-0.77) had a sensitivity of 63.6% and a specificity of 61.8% to detect pAF. The combination of both markers enhanced the validity of pAF detection sensitivity to 89.6%, with a specificity of 27.59%. These patients had increased risk of pAF during the 90-day monitoring HR 3.23 (χ2 7.15) and beyond 90 days (χ2 5.37). Intensive 90-days TWH monitoring detected a high percentage of pAF. However, a significant number of patients did not complete the monitoring. Patients older than 70 years and with enlarged left atria benefitted more from the protocol.

Red Ear and More: Facial and Extrafacial Erythema Accompanying Migraine Attacks.

Cutaneous manifestations of migraine are infrequent and their spectrum is reduced to the red ear syndrome (RES) and eyelid disorders. We report a case of a 26-year-old woman with migraine accompanied by extensive erythema, which involved right ear and cheek and left hemithorax. She fulfilled proposed criteria of RES. We started preventive therapy with a significant response. This is the first description in the literature of an erythema accompanying migraine attacks broadly exceeding the ear.

[Medullary infarction secondary to endovascular treatment of thoracoabdominal aortic aneurysm] / Infarto medular secundario a tratamiento endovascular de aneurisma de aorta toraco-abdominal.

Medullary infarction is a severe and infrequent pathology, which represents 1% of all ischemic strokes, and is also a rare complication of different surgical procedures. It is caused by the acute interruption of the blood flow of the spinal cord, manifesting itself with clinical neurological deficits related to the affected vascular territory. Methods: We present the case of an 80-year-old patient, with cardiovascular risk factors, who is present on post-surgical day 13, after placement of a vascular endoprosthesis for a thoracoabdominal aneurysm, sudden appearance of paraparesis with progression to paraplegia and hypoesthesia in both lower extremities. CT angiography of the aorta rules out local complications in the endoprosthesis. Medullary MRI showed images compatible with acute dorsal medullary infarction from level D9. Results: On discharge, the patient presented paraplegia and hypoesthesia of both lower extremities with fecal and urinary incontinence. Conclusion: Spinal cord infarction may be limited to a vascular territory or be more extensive according to its pathogenesis. The affectation of the anterior spinal artery is the most common and is characterized by bilateral motor deficits and loss of thermoalgesic sensitivity, which could have a great impact on the quality of life of patients. Its etiology is varied, including aortic surgery within its causes. MRI is very useful for its diagnosis and currently there are no clinical guides for the optimal treatment.

Introducción: El infarto medular es una patología severa e infrecuente, que representa el 1% del total de ictus isquémicos, siendo además una complicación rara de distintos procedimientos quirúrgicos. Es causado por la interrupción aguda del flujo sanguíneo de la médula espinal, manifestándose con déficits neurológicos clínicos relacionados con el territorio vascular afectado. Métodos: Presentamos el caso de un paciente de 80 años, con factores de riesgo cardiovascular, quien presenta en día postquirúrgico 13, tras colocación de endoprótesis vascular por aneurisma toraco-abdominal aparición brusca de paraparesia con progresión a paraplejía e hipoestesia en ambas extremidades inferiores.  Angio-TC de aorta descarta complicación local en la endoprótesis. RM medular mostró imágenes compatibles con Infarto agudo de médula dorsal desde el nivel D9. El paciente no fue subsidiario de tratamiento revascularizador. El tratamiento consistió en medidas de soporte. Resultados: Al alta el paciente presentaba paraplejia e hipoestesia de ambas extremidades inferiores con incontinencia fecal y urinaria. Conclusión: El infarto de la médula espinal puede estar limitado a un territorio vascular o estar más extendido según su patogenia. La afectación de la arteria espinal anterior es la más común y se caracteriza por déficits motores bilaterales y pérdida de la sensibilidad termoalgésica, pudiendo llegar a producir un gran impacto en la calidad de vida de los pacientes. Su etiología es variada, incluyéndose la cirugía aórtica dentro de sus causas. La RM es muy útil para su diagnóstico y actualmente no existen guías clínicas para el tratamiento óptimo.

Endoscopic third ventriculostomy limited by artery of Percheron.

The irrigation of the thalamus depends mainly on the thalamoperforating arteries. There are many anatomical variations in these arteries, the best known being the artery of Percheron. We report a case of a 13-year-old male presented with headache and decline in his mental status. Imaging features showed obstructive hydrocephalus secondary to a mass at the level of the mesencephalon so an endoscopic third ventriculostomy was performed. During the procedure a thalamoperforating artery was encountered at the level of the tuber cinereum limiting the perforation of the third ventricle floor. The present case emphasizes the importance of knowing the anatomy of these arteries and the identification of their main variants during neurosurgical procedures.

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 < .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.

Decompressive Craniectomy in Pregnant Women.

Malignant middle cerebral artery (MCA) infarction warranting decompressive craniectomy (DC) is unusual in the population younger than 40 years. Specifically, only a few cases affecting pregnant women have been described in the literature. We present the case of a 39-year-old woman in the 24th week of pregnancy who suffered a right malignant MCA infarction that eventually required DC. The patient delivered a healthy baby and underwent a second surgery for cranioplasty 7 months later. We present both this case and a review of the literature, including all cases of DC in pregnant women published to date.

Proteins and pathways in atrial fibrillation and atrial cardiomyopathy underlying cryptogenic stroke.

Background: Atrial fibrillation (AF) is one of the most prevalent causes of cryptogenic stroke. Also, apart from AF itself, structural and remodelling changes in the atria might be an underlying cause of cryptogenic stroke. We aimed to discover circulating proteins and reveal pathways altered in AF and atrial cardiomyopathy, measured by left atrial volume index (LAVI) and peak atrial longitudinal strain (PALS), in patients with cryptogenic stroke. Methods: An aptamer array (including 1310 proteins) was measured in the blood of 20 cryptogenic stroke patients monitored during 28 days with a Holter device as a case-control study of the Crypto-AF cohort. Protein levels were compared between patients with (n = 10) and without AF (n = 10) after stroke, and the best candidates were tested in 111 patients from the same cohort (44 patients with AF and 67 without AF). In addition, in the first 20 patients, proteins were explored according to PALS and LAVI values. Results: Forty-six proteins were differentially expressed in AF cases. Of those, four proteins were tested in a larger sample size. Only DPP7, presenting lower levels in AF patients, was further validated. Fifty-seven proteins correlated with LAVI, and 270 correlated with PALS. NT-proBNP was common in all the discovery analyses performed. Interestingly, many proteins and pathways were altered in patients with low PALS. Conclusions: Multiple proteins and pathways related to AF and atrial cardiomyopathy have been revealed. The role of DPP7 as a biomarker for stroke aetiology should be further explored. Moreover, the present study may be considered hypothesis-generating.

Blood-Based Biomarkers to Search for Atrial Fibrillation in High-Risk Asymptomatic Individuals and Cryptogenic Stroke Patients.

Background: Atrial fibrillation (AF) increases the risk of ischemic stroke in asymptomatic individuals and may be the underlying cause of many cryptogenic strokes. We aimed to test the usefulness of candidate blood-biomarkers related to AF pathophysiology in two prospective cohorts representative of those populations. Methods: Two hundred seventy-four subjects aged 65-75 years with hypertension and diabetes from the AFRICAT cohort, and 218 cryptogenic stroke patients aged >55 years from the CRYPTO-AF cohort were analyzed. AF was assessed by 4 weeks of monitoring with a wearable Holter device (NuuboTM™). Blood was collected immediately before monitoring started. 10 candidate biomarkers were measured by automated immunoassays (Roche, Penzberg) in the plasma of all patients. Univariate and logistic regression analyses were performed in each cohort separately. Results: Atrial fibrillation detection rate was 12.4% (AFRICAT cohort) and 22.9% (CRYPTO-AF cohort). 4 biomarkers were significantly increased in asymptomatic individuals with AF [Troponin-T, Angiopoietin-2 (Ang-2), Endocan, and total N-terminal pro-B type natriuretic peptide (NT-proBNP)] and 7 biomarkers showed significantly higher concentrations in cryptogenic stroke patients with AF detection [growth differentiation factor 15, interleukin 6, Troponin-T, Ang-2, Bone morphogenic protein 10, Dickkopf-related protein 3 (DKK-3), and total NT-proBNP]. The models including Ang-2 and total NT-proBNP [AUC 0.764 (0.665-0.863)], and Ang-2 and DKK-3 [AUC = 0.733 (0.654-0.813)], together with age and sex, showed the best performance to detect AF in high-risk asymptomatic individuals, and in cryptogenic stroke patients, respectively. Conclusion: Blood-biomarkers, in particular, total NT-proBNP, DKK-3, and Ang-2, were associated with AF reflecting two mechanistically different pathways involved in AF pathophysiology (AF stretch and vascular changes). The combination of these biomarkers could be useful in AF screening strategies in the primary care setting and also for searching AF after cryptogenic stroke.

Predicting Atrial Fibrillation with High Risk of Embolization with Atrial Strain and NT-proBNP.

The aim of the study was to determine markers of atrial dysfunction in patients with cryptogenic stroke to predict episodes of paroxysmal atrial fibrillation with high risk of embolization (HpAF). We classified patients included in the Crypto-AF study, Cryptogenic Stroke registry, to detect paroxysmal atrial fibrillation (pAF) with wearable Holter, according to the longest episode of pAF in three groups: without pAF detection, episodes of pAF shorter than 5 h, and episodes of pAF longer than 5 h (HpAF). Atrial dysfunction surrogates were evaluated: EKG pattern, Holter record and echocardiography parameters (left atria volume (LAVI), and peak atrial longitudinal and contraction strain (PALS and PACS). The level of N-terminal pro b-type natriuretic peptide (NT-proBNP) was determined. All patients were followed for 2 years to detect pAF and stroke recurrence. From 308 patients, 253 patients with high quality Holter analysis were selected. The distribution was No pAF 78.6% (n = 199), pAF < 5 h 7.9% (n = 20), and HpAF > 5 h 13.4% (n = 34). Age of the patients and combination of PALS and NT-proBNP independently predicted HpAF OR 1.07 (1.00; 1.15) and OR 3.05 (1.08; 8.60) respectively. The validity of PALS and NT-proBNP to detect patients at risk of HpAF was higher than the validity of age (AUC 0.82, sensitivity 78.95%, specificity 63%). Patients with PALS < 25% and NT-proBNP > 283 pg/ml had more detection of pAF during follow-up 35% vs. 5.1% OR 2.33 (1.05-5.13) (p < 0.001). Multimodal assessment of atrial dysfunction with PALS and NT-proBNP improved the prediction of pAF episodes with high embolic risk in patients with cryptogenic stroke.

The Neuronal Ischemic Tolerance Is Conditioned by the Tp53 Arg72Pro Polymorphism.

Cerebral preconditioning (PC) confers endogenous brain protection after stroke. Ischemic stroke patients with a prior transient ischemic attack (TIA) may potentially be in a preconditioned state. Although PC has been associated with the activation of pro-survival signals, the mechanism by which preconditioning confers neuroprotection is not yet fully clarified. Recently, we have described that PC-mediated neuroprotection against ischemic insult is promoted by p53 destabilization, which is mediated by its main regulator MDM2. Moreover, we have previously described that the human Tp53 Arg72Pro single nucleotide polymorphism (SNP) controls susceptibility to ischemia-induced neuronal apoptosis and governs the functional outcome of patients after stroke. Here, we studied the contribution of the human Tp53 Arg72Pro SNP on PC-induced neuroprotection after ischemia. Our results showed that cortical neurons expressing the Pro72-p53 variant exhibited higher PC-mediated neuroprotection as compared with Arg72-p53 neurons. PC prevented ischemia-induced nuclear and cytosolic p53 stabilization in Pro72-p53 neurons. However, PC failed to prevent mitochondrial p53 stabilization, which occurs in Arg72-p53 neurons after ischemia. Furthermore, PC promoted neuroprotection against ischemia by controlling the p53/active caspase-3 pathway in Pro72-p53, but not in Arg72-p53 neurons. Finally, we found that good prognosis associated to TIA within 1 month prior to ischemic stroke was restricted to patients harboring the Pro72 allele. Our findings demonstrate that the Tp53 Arg72Pro SNP controls PC-promoted neuroprotection against a subsequent ischemic insult by modulating mitochondrial p53 stabilization and then modulates TIA-induced ischemic tolerance.