https://www.ahajournals.org/doi/pdf/10.1161/STR.0000000000000375

2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association

Epidemiological evidence suggests that the incidence of ischaemic stroke in young adults (18-50 years) has increased substantially. These patients have a long life expectancy after stroke, and the costs of long-term care pose huge challenges to health-care systems. Although the current recommendations for treatment of young and old (>50 years) patients with stroke are similar, the optimal management of young adult patients with stroke is unknown. They are usually not included in trials, and specific subanalyses limited to young adult patients with stroke are usually not done, owing to lower incidence of stroke and lower prevalence of vascular risk factors in young adults. Progress has been made in identifying patients with a considerable risk of stroke occurrence, such as those with patent foramen ovale. Future prevention studies might result in a decrease in the incidence of stroke and its sequelae in young adults. The development of guidelines specifically devoted to the management of stroke in young adults will be an important step in achieving this aim.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(18)30233-3.pdf

Epidemiology, aetiology, and management of ischaemic stroke in young adults

Background Fabry Disease (FD), an X linked lysosomal storage disease due to pathogenic α-galactosidase A ( GLA ) mutations, results in two major subtypes, the early-onset Type 1 ‘Classic’ and the Type 2 ‘Later-Onset’ phenotypes. To identify previously unrecognised patients, investigators screened cardiac, renal and stroke clinics by enzyme assays. However, some screening studies did not perform confirmatory GLA mutation analyses, and many included recently recognised ‘benign/likely-benign’ variants, thereby inflating prevalence estimates. Methods Online databases were searched for all FD screening studies in high-risk clinics (1995–2017). Studies reporting GLA mutations were re-analysed for pathogenic mutations, sex and phenotype. Phenotype-specific and sex-specific prevalence rates were determined. Results Of 67 studies, 63 that screened 51363patients (33943M and 17420F) and provided GLA mutations were reanalysed for disease-causing mutations. Of reported GLA mutations, benign variants occurred in 47.9% of males and 74.1% of females. The following were the revised prevalence estimates: among 36820 (23954M and 12866F) haemodialysis screenees, 0.21% males and 0.15% females; among 3074 (2031M and 1043F) renal transplant screenees, 0.25% males and no females; among 5491 (4054M and 1437F) cardiac screenees, 0.94% males and 0.90% females; and among 5978 (3904M and 2074F) stroke screenees, 0.13% males and 0.14% females. Among male and female screenees with pathogenic mutations, the type 1 Classic phenotype was predominant (~60%), except more male cardiac patients (75%) had type 2 Later-Onset phenotype. Conclusions Compared with previous findings, reanalysis of 63 studies increased the screenee numbers (~3.4-fold), eliminated 20 benign/likely benign variants, and provided more accurate sex-specific and phenotype-specific prevalence estimates, ranging from ~0.13% of stroke to ~0.9% of cardiac male or female screenees.

Fabry Disease: prevalence of affected males and heterozygotes with pathogenic GLA mutations identified by screening renal, cardiac and stroke clinics, 1995–2017

Purpose of review This article reviews current knowledge on epidemiology, risk factors and causes, diagnostic considerations, management, and prognosis of ischemic stroke in young adults (those 55 years old and younger). Recent findings The incidence of ischemic stroke in young adults has been increasing since the 1980s, which has occurred in parallel with increasing prevalence of vascular risk factors and substance abuse among the younger population. Young adults have a considerably wider range of risk factors than older patients, including age-specific factors such as pregnancy/puerperium and oral contraceptive use. Behavioral risk factors such as low physical activity, excess alcohol consumption, and smoking are factors as well. More than 150 identified causes of early-onset ischemic stroke exist, including rare monogenic disorders. Several recent advances have been made in diagnosis and management of stroke in young adults, including molecular characterization of monogenic vasculitis due to deficiency of adenosine deaminase 2 and transcatheter closure of patent foramen ovale for secondary prevention. Compared with the background population of the same age and sex, long-term mortality in patients remains fourfold higher with cardiovascular causes underlying most of the deaths. The cumulative rate of recurrent stroke extends up to 15% at 10 years. Patients with atherosclerosis, high-risk sources of cardioembolism, and small vessel disease underlying their stroke seem to have the worst prognosis regarding survival and recurrent vascular events. Young stroke survivors also often have other adverse outcomes in the long term, including epilepsy, pain, cognitive problems, and depression. Summary Systematic identification of risk factors and causes and the motivation of patients for long-term prevention and lifestyle changes are of utmost importance to improve the prognosis of early-onset ischemic stroke.

/pdf/ischemic-stroke-in-young-adults-3svxu9wntd.pdf

Ischemic Stroke in Young Adults.

CADASIL is a life-threatening and disabling disease. Despite the progress achieved so far, no therapies able to limit the disease progression have been found and only empiric treatments can be employed to relieve the main disease symptoms. Further in vivo studies as well as data aggregation and multi-centre controlled clinical trials are needed to confirm the emerging findings in order to identify evidence-based therapies for CADASIL.

CADASIL: Treatment and Management Options.

Background and Purpose— Lombardia GENS is a multicentre prospective study aimed at diagnosing 5 single-gene disorders associated with stroke (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Fabry disease, MELAS [mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes], hereditary cerebral amyloid angiopathy, and Marfan syndrome) by applying diagnostic algorithms specific for each clinically suspected disease

Methods— We enrolled a consecutive series of patients with ischemic or hemorrhagic stroke or transient ischemic attack admitted in stroke units in the Lombardia region participating in the project. Patients were defined as probable when presenting with stroke or transient ischemic attack of unknown etiopathogenic causes, or in the presence of <3 conventional vascular risk factors or young age at onset, or positive familial history or of specific clinical features. Patients fulfilling diagnostic algorithms specific for each monogenic disease (suspected) were referred for genetic analysis.

Results— In 209 patients (57.4±14.7 years), the application of the disease-specific algorithm identified 227 patients with possible monogenic disease. Genetic testing identified pathogenic mutations in 7% of these cases. Familial history of stroke was the only significant specific feature that distinguished mutated patients from nonmutated ones. The presence of cerebrovascular risk factors did not exclude a genetic disease.

Conclusions— In patients prescreened using a clinical algorithm for monogenic disorders, we identified monogenic causes of events in 7% of patients in comparison to the 1% to 5% prevalence reported in previous series.

Maurizio Ferrari

Papers

Clinical Pregenetic Screening for Stroke Monogenic Diseases: Results From Lombardia GENS Registry