Asociación entre calcificaciones de la glándula pineal y enfermedad aterosclerótica intracraneal en adultos mayores

Background: This study assesses whether pineal gland calcification (PGC) – a surrogate for reduced endogenous melatonin production – is associated with significant stenosis of large intracranial arteries – a biomarker of intracranial atherosclerotic disease (ICAD). Methods: Individuals aged ≥60 years enrolled in the Three Villages Study received head CT to assess PGC and MRA to estimate stenosis of large intracranial arteries. Multivariate logistic regression models were fitted to assess the association between PGC and ICAD, after adjusting for relevant confounders. Inverse probability of exposure weighting was used to estimate the effect of PGC on ICAD. Results: A total of 581 individuals were enrolled. PGC and ICAD were associated in a fully-adjusted logistic regression model (p=0.032). Inverse probability of exposure weighting showed an estimate for the proportion of ICAD among those without PGC of 3.7% and the adjusted-effect coefficient was 5.7% higher among those with PGC (p=0.031). Conclusions: PGC is associated with ICAD. Study results provide grounds for evaluating the role of melatonin deficiency in ICAD progression. Keywords: Pineal gland calcification, intracranial atherosclerosis, stenosis of large intracranial arteries, melatonin; population study, older adults

Balloon expandable Stent utility for early Secondary Prevention of new Cerebral Ischemic events Caused by Intracranial Atherosclerotic Stenosis. Technical Nuances

Objective: Recurrent cerebral ischemic events are estimated to appear in between 12-15% of symptomatic intracranial atherosclerotic disease (ICAD), regardless of the use of leading pharmacological therapies. Balloon expandable stent (balloon mounted coronary stent) could represent a feasible alternative in this disease’s treatment. This study pretends to report the balloon-expandable placement experience in our center. Materials and Methods: A unicentric retrospective study dated between September 2009 and March 2018 was conducted. Patients previously diagnosed with ICAD and symptomatic stenosis treated with balloon-expandable stent were included. Clinical features, morbidity, mortality, short and long-term evolution, and pre-and post-treatment angiographic features were analyzed, as well as a mean 8 years-period follow-up. Data are presented as means, frequencies, and percentages for categorical variables, and ranks for continuous variables. Statistical analysis was carried by IBM SPSS Statistics Base V22.0 (IBM Corporation, Mexico). A Wilcoxon Signed-rank test statistical analysis was performed. Statistical significance was considered when a p-value lesser than 0.05 was measured for every result. Results: A total of 6 patients with 7 affected vessels were treated, with an average age of 62.7 years. Affected and treated vessels were located in the Internal Carotid Artery (ICA) segment in 42.9%, Vertebral Artery (VA) V4 segment in 14.3%, Middle Cerebral Artery (MCA) M1 segment in 28.5%, and Posterior Cerebral Artery (PCA) P1 segment in 14.3%. The incidence of peri-operatory thrombotic events was 0%. Intracranial hemorrhage presented in 0% of cases. Recurrent ischemic or thrombotic events were not reported in a 97-months mean follow-up. 71.4% of patients scored ≤2 in the modified Rankin Score (mRS) pre-treatment, in a 90 day and 12-month follow-up. 100% presented a favorable evolution with mRS ≤2. Restenosis cases were not reported in radiologic control and retreatment was not needed in a 97-month mean follow-up. Conclusions: This study suggests that balloon-expandable stent therapy with some technical endovascular variants for its navigation and placement could be a safe and effective alternative in the treatment of ICAD as a means of cerebral ischemic event early secondary prevention. We propose to consider not to limit endovascular treatment exclusively to those symptomatic ICAD patients refractory to medical-exclusive treatment, as a means to reduce the risk of presenting a new neurological deficit. Further expanded clinical trials are needed to confirm these findings and the advantage of this kind of stents against other kinds reported in the literature.

Intracranial atherosclerosis: Review of imaging features and advances in diagnostics

Intracranial atherosclerotic disease is one of the leading causes of ischemic strokes and poses a moderate risk of recurrence. Diagnosis is currently limited to stenosis on luminal imaging, which likely underestimates the true prevalence of the disease. Detection of non-stenosing intracranial atherosclerosis is important in order to optimize secondary stroke prevention strategies. This review collates findings from the early seminal trials and the latest studies in advanced radiological techniques that characterize symptomatic intracranial atherosclerotic disease across various imaging modalities. While computed tomography angiography (CTA) and magnetic resonance angiography (MRA) comprise diagnostic mainstays in identifying stenotic changes secondary to atherosclerosis, emerging techniques such as high-resolution MRA, quantitative MRA, and computational fluid dynamics may reveal a myriad of other underlying pathophysiological mechanisms.

Genome sequencing reveals the role of rare genomic variants in Chinese patients with symptomatic intracranial atherosclerotic disease

ObjectivesThe predisposition of intracranial atherosclerotic disease (ICAD) to East Asians over Caucasians infers a genetic basis which, however, remains largely unknown. Higher prevalence of vascular risk factors (VRFs) in Chinese over Caucasian patients who had a stroke, and shared risk factors of ICAD with other stroke subtypes indicate genes related to VRFs and/or other stroke subtypes may also contribute to ICAD.MethodsUnrelated symptomatic patients with ICAD were recruited for genome sequencing (GS, 60-fold). Rare and potentially deleterious single-nucleotide variants (SNVs) and small insertions/deletions (InDels) were detected in genome-wide and correlated to genes related to VRFs and/or other stroke subtypes. Rare aneuploidies, copy number variants (CNVs) and chromosomal structural rearrangements were also investigated. Lastly, candidate genes were used for pathway and gene ontology enrichment analysis.ResultsAmong 92 patients (mean age at stroke onset 61.0±9.3 years), GS identified likely ICAD-associated rare genomic variants in 54.3% (50/92) of patients. Forty-eight patients (52.2%, 48/92) had 59 rare SNVs/InDels reported or predicted to be deleterious in genes related to VRFs and/or other stroke subtypes. None of the 59 rare variants were identified in local subjects without ICAD (n=126). 31 SNVs/InDels were related to conventional VRFs, and 28 were discovered in genes related to other stroke subtypes. Our study also showed that rare CNVs (n=7) and structural rearrangement (a balanced translocation) were potentially related to ICAD in 8.7% (8/92) of patients. Lastly, candidate genes were significantly enriched in pathways related to lipoprotein metabolism and cellular lipid catabolic process.ConclusionsOur GS study suggests a role of rare genomic variants with various variant types contributing to the development of ICAD in Chinese patients.

Intracranial Atherosclerotic Disease

Purpose of the ReviewThis article reviews the current concepts in intracranial atherosclerotic disease (ICAD) as a common etiology of ischemic stroke; pathophysiologic mechanisms of ischemic stroke; diagnostic evaluation; and therapeutic modalities, including maximal medical therapy (MMT), percutaneous transluminal angioplasty and stenting (PTAS), and bypass surgery.Recent FindingsData from recent studies demonstrate that proper patient selection and timing of procedure and standardized PTAS techniques by experienced operators resulted in acceptably low periprocedural adverse events for patients who failed MMT.SummaryICAD is a common cause of ischemic stroke. Complex pathology and high rates of recurrent and disabling ischemic strokes despite currently available treatments make ICAD the most challenging to treat of all ischemic stroke etiologies. Randomized trials previously showed that MMT, which involves the use of combinations of antiplatelet medications, targeted control of hypertension and serum low-density lipoprotein cholesterol, and adequate management of body weight through lifestyle modification, was superior to PTAS in decreasing rates of recurrent ischemic strokes from symptomatic ICAD. MMT performed better than expected, while periprocedural complications were significantly higher than expected in PTAS. Meanwhile, high rates of recurrent ischemic stroke despite MMT remain a great challenge. New clinical evidence continues to emerge on a safer application of PTAS, which is currently offered to a subset of patients who present with recurrent ischemic strokes despite MMT.

Abstract 1122‐000125: Underlying ICAD is Associated with Worse Outcome in Acute Large Vessel Occlusion Undergoing Endovascular Therapy

Introduction : Acute large vessel occlusion (LVO) can be secondary to thromboembolism or underlying intracranial atherosclerotic disease (ICAD). Data on the management of LVO due to underlying ICAD are scarce. We hypothesized that patients with ICAD would have worse clinical outcomes following mechanical thrombectomy (MT) than those without ICAD. Methods : We performed a retrospective analysis of consecutive patients who underwent MT for LVO in a large academic comprehensive stroke center between 01/2018 and 05/2021. Presence of underlying ICAD at the site of LVO was determined by the treating interventionalist. We compared outcomes including in‐hospital mortality and 90‐day modified Rankin Scale (mRS) between those with and without underlying ICAD, adjusting for relevant covariates using logistic regression. Results : Among 195 patients (mean age 67.4+15.1 years, 56.9% female, 81% black, median NIHSS score 15), underlying ICAD was present in 39 (20.0%). Stent‐retrievers were used 196 patients with only 3 having rescue stent placement. There were no significant differences in baseline factors amongst the two groups except diabetes was more common (69.2% vs. 49.7%, p = 0.028) and intravenous thrombolysis provided less often (17.9% vs. 36.5%, p = 0.027) in those with ICAD. TICI 2B or higher was achieved in 82.1% of ICAD compared with 94.3% of non‐ICAD patients (p = 0.012). Mortality was more common (50.0% vs. 30.8%, p = 0.025) and good functional outcome (mRS 0–2) at 90 days was less common (10.8% vs. 30.0%, p = 0.002) in the ICAD group. Adjusting for age, diabetes, intravenous thrombolysis, baseline NIHSS score, and final TICI score, underlying ICAD was an independent predictor of mRS 0–2 at 90 days (OR 4.5, 95% CI 1.4‐14.2, p = 0.010). Conclusions : Underlying ICAD is associated with 4.5‐fold increase in poor functional outcome in patients with LVO undergoing traditional MT. Further research is needed to understand factors associated with poor outcomes investigate alternative interventional approaches and medical management in this high‐risk population.