High Prevalence of Atrial Fibrillation in a Lithuanian Stroke Patient Cohort.

Background and Objectives: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a five-fold increased risk for acute ischemic stroke (AIS). We aimed to estimate the prevalence of AF in a Lithuanian cohort of stroke patients, and its impact on patients regarding case fatality, functional outcome, and health-related quality of life (HRQoL) at 90 days. Materials and Methods: A single-center prospective study was carried out for four non-consecutive months between December 2018 and July 2019 in one of the two comprehensive stroke centers in Eastern Lithuania. A telephone-based follow-up was conveyed at 90 days using the modified Rankin Scale (mRS) and EuroQoL five-dimensional three-level descriptive system (EQ-5D-3L) with a self-rated visual analog scale (EQ-VAS). One-year case fatality was investigated. Results: We included 238 AIS patients with a mean age of 71.4 ± 11.9 years of whom 45.0% were female. A striking 97 (40.8%) AIS patients had a concomitant AF, in 68 (70.1%) of whom the AF was pre-existing. The AIS patients with AF were at a significantly higher risk for a large vessel occlusion (LVO; odds ratio 2.72 [95% CI 1.38−5.49], p = 0.004), and had a more severe neurological impairment at presentation (median NIHSS score (interquartile range): 9 (6−16) vs. 6 (3−9), p < 0.001). The LVO status was only detected in those who had received computed tomography angiography. Fifty-five (80.9%) patients with pre-existing AF received insufficient anticoagulation at stroke onset. All patients received a 12-lead ECG, however, in-hospital 24-h Holter monitoring was only performed in 3.4% of AIS patients without pre-existing AF. Although multivariate analyses found no statistically significant difference in one-year stroke patient survival and favorable functional status (mRS 0−2) at 90 days, when adjusted for age, gender, reperfusion treatment, baseline functional status, and baseline NIHSS, stroke patients with AF had a significantly poorer self-perceived HRQoL, indicated by a lower EQ-VAS score (regression coefficient ± standard error: ß = −11.776 ± 4.850, p = 0.017). Conclusions: In our single-center prospective observational study in Lithuania, we found that 40.8% of AIS patients had a concomitant AF, were at a higher risk for an LVO, and had a significantly poorer self-perceived HRQoL at 90 days. Despite the high AF prevalence, diagnostic tools for subclinical AF were greatly underutilized.

Ischemic Stroke Genetics: What Is New and How to Apply It in Clinical Practice?

The etiology of ischemic stroke is multifactorial. Although receiving less emphasis, genetic causes make a significant contribution to ischemic stroke genesis, especially in early-onset stroke. Several stroke classification systems based on genetic information corresponding to various stroke phenotypes were proposed. Twin and family history studies, as well as candidate gene approach, are common methods to discover genetic causes of stroke, however, both have their own limitations. Genome-wide association studies and next generation sequencing are more efficient, promising and increasingly used for daily diagnostics. Some monogenic disorders, despite covering only about 7% of stroke etiology, may cause well-known clinical manifestations that include stroke. Polygenic disorders are more frequent, causing about 38% of all ischemic strokes, and their identification is a rapidly developing field of modern stroke genetics. Current advances in human genetics provide opportunity for personalized prevention of stroke and novel treatment possibilities. Genetic risk scores (GRS) and extended polygenic risk scores (PRS) estimate cumulative contribution of known genetic factors to a specific outcome of stroke. Combining those scores with clinical information and risk factor profiles might result in better primary stroke prevention. Some authors encourage the use of stroke gene panels for stroke risk evaluation and further stroke research. Moreover, new biomarkers for stroke genetic causes and novel targets for gene therapy are on the horizon. In this article, we summarize the latest evidence and perspectives of ischemic stroke genetics that could be of interest to the practitioner and useful for day-to-day clinical work.

Novel In-Frame Deletion in HTRA1 Gene, Responsible for Stroke at a Young Age and Dementia-A Case Study.

Biallelic mutations in the high-temperature requirement A serine peptidase 1 (HTRA1) gene are known to cause an extremely rare cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), which belongs to the group of hereditary cerebral small vessel diseases and is mainly observed in the Japanese population. Even though this pathology is inherited in an autosomal recessive manner, recent studies have described symptomatic carriers with heterozygous HTRA1 mutations who have milder symptoms than patients with biallelic HTRA1 mutations. We present the case of a Lithuanian male patient who had a stroke at the age of 36, experienced several transient ischemic attacks, and developed an early onset, progressing dementia. These clinical symptoms were associated with extensive leukoencephalopathy, lacunar infarcts, and microbleeds based on brain magnetic resonance imaging (MRI). A novel heterozygous in-frame HTRA1 gene deletion (NM_002775.5:c.533_535del; NP_002766.1:p.(Lys178del)) was identified by next generation sequencing. The variant was consistent with the patient's phenotype, which could not be explained by alternative causes, appeared highly deleterious after in silico analysis, and was not reported in the medical literature or population databases to date.