Background: In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain. Methods: This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment. Results: After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA ₂ DS ₂ -VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase; P =0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1]; P =0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase; P =0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2]; P =0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5]; P =0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]). Conclusions: Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.

Assessing ischemic etiology and mechanism during the acute phase of an ischemic stroke is crucial in order to tailor and monitor appropriate treatment and determine prognosis. Cervical Duplex Ultrasound (CDU) has evolved since many years as an excellent screening tool for the evaluation of extracranial vasculature. CDU has the advantages of a low cost, easily applicable, bed side examination with high temporal and spatial resolution and without exposing the patients to any significant complications. It represents an easily repeatable test that can be performed in the emergency room as a first-line examination of cervical artery pathology. CDU provides well validated estimates of the type of the atherosclerotic plaque, the degree of stenosis, as well as structural and hemodynamic information directly about extracranial vessels (e.g., subclavian steal syndrome) and indirectly about intracranial circulation. CDU may also aid the diagnosis of non-atherosclerotic lesions of vessel walls including dissections, arteritis, carotid-jugular fistulas and fibromuscular dysplasias. The present narrative review outlines all potential applications of CDU in acute stroke management and also highlights its potential therapeutic implications.

BACKGROUND: Atrial fibrillation (AF) is a frequent underlying cause of cryptogenic stroke (CS) and its detection can be increased using implantable cardiac monitoring (ICM). We sought to evaluate different risk scores and assess their diagnostic ability in identifying patients with CS with underlying AF on ICM. METHODS: Patients with CS, being admitted to a single tertiary stroke center between 2017 and 2022 and receiving ICM, were prospectively evaluated. The CHA ₂ DS ₂ -VASc, HAVOC, Brown ESUS-AF, and C ₂ HEST scores were calculated at baseline. The primary outcome of interest was the detection of AF, which was defined as at least 1 AF episode on ICM lasting for 2 consecutive minutes or more. The diagnostic accuracy measures and the net reclassification improvement were calculated for the 4 risk scores. Stroke recurrence was evaluated as a secondary outcome. RESULTS: A total of 250 patients with CS were included, and AF was detected by ICM in 20.4% (n=51) during a median monitoring period of 16 months. Patients with CS with AF detection were older compared with the rest ( P =0.045). The median HAVOC, Brown ESUS-AF, and C ₂ HEST scores were higher among the patients with AF compared with the patients without AF (all P <0.05), while the median CHA ₂ DS ₂ -VASc score was similar between the 2 groups. The corresponding C statistics for CHA ₂ DS ₂ -VASc, HAVOC, Brown ESUS-AF, and C ₂ HEST for AF prediction were 0.576 (95% CI, 0.482–0.670), 0.612 (95% CI, 0.523–0.700), 0.666 (95% CI, 0.587–0.746), and 0.770 (95% CI, 0.699–0.839). The C ₂ HEST score presented the highest diagnostic performance based on C statistics ( P 70%) compared with the other risk scores. Finally, stroke recurrence was documented in 5.6% of the study population, with no difference regarding the 4 risk scores between patients with and without recurrent stroke. CONCLUSIONS: The C ₂ HEST score was superior to the CHA ₂ DS ₂ -VASc, HAVOC, and Brown ESUS-AF scores for discriminating patients with CS with underlying AF using ICM.

Lipoprotein(a) [Lp(a)] has attracted widespread interest as a potential biomarker for cerebrovascular diseases due to its genetically determined and stable plasma concentration throughout life. Lp(a) exhibits pro-atherogenic and pro-thrombotic properties that contribute to vascular pathology in both extracranial and intracranial vessels. Elevated Lp(a) levels are strongly associated with large-artery atherosclerotic stroke, while data on its role in other ischemic subtypes and hemorrhagic stroke remains limited and inconsistent. Recent advances in Lp(a)-lowering therapies, such as antisense oligonucleotides and RNA-based agents, have demonstrated significant efficacy in reducing plasma Lp(a) levels. These advances have prompted increasing research into their potential application in the prevention and treatment of cerebrovascular diseases, aiming to determine whether Lp(a) reduction may translate into a reduced risk of stroke and large-artery atherosclerosis. This narrative review summarizes the current evidence on the association between Lp(a) and stroke, focusing on its utility in patient risk stratification. It also highlights existing knowledge gaps and outlines directions for future research, particularly in understanding subtype-specific effects and evaluating the clinical benefits of Lp(a)-targeted therapies.

Background: Alzheimer’s disease (AD) is the most common cause of dementia. In addition to cognitive decline, non-cognitive symptoms, including dysautonomia, have been reported, although these symptoms are rarely acknowledged by patients. Dysautonomia in AD is thought to arise from either cholinergic deficits or hypothalamic involvement. A wide range of tests has been used to investigate the role of the autonomic nervous system; however, the results have been inconsistent. Aim: To systematically review all published research investigating autonomic nervous system (ANS) involvement in patients with AD. A comprehensive literature search was conducted in December 2024 across the following databases: PubMed, Cochrane Library, ScienceDirect, and Scopus. Results: A total of 1422 records were identified, of which 30 studies fulfilled the inclusion criteria and were included in the review. Several autonomic tests were employed, with Heart Rate Variability (HRV) being the most frequently used. Other tests included assessments of orthostatic hypotension (OH), postprandial hypotension (PPH), sympathetic skin response (SSR), the tilt test, 123I-MIBG cardiac scintigraphy, norepinephrine (NE) measurements in serum and cerebrospinal fluid, and baroreflex sensitivity. In most studies, AD patients were compared to either healthy controls or patients with other types of dementia. Discussion: The primary finding of this review is that, although patients with AD rarely report dysautonomic symptoms, they frequently exhibit abnormal results on various autonomic tests. In some cases, these findings were sufficient to differentiate AD patients from healthy controls as well as from patients with Diffuse Lewy Body disease (DLB). The inconsistency in reporting symptoms, along with the variability in test results, suggests that autonomic dysfunction in AD may be under-recognized and warrants further investigation. Conclusions: The heterogeneity of the included studies limits the generalizability of the results. However, given the potential impact of dysautonomia on both quality of life and mortality, it is recommended that AD patients be systematically assessed for autonomic dysfunction. Even in the absence of overt symptoms, appropriate treatment should be considered where indicated to mitigate potential risks.