Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design

Background: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient– control pairs enrolled by the end of 2018. Summary: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019

Obesity and the Risk of Cryptogenic Ischemic Stroke in Young Adults

Objectives: We examined the association between obesity and early-onset cryptogenic ischemic stroke (CIS) and whether fat distribution or sex altered this association. Materials and Methods: This prospective, multi-center, case-control study included 345 patients, aged 18-49 years, with first-ever, acute CIS. The control group included 345 age-and sex-matched stroke-free individuals. We measured height, weight, waist circumference, and hip circumference. Obesity metrics analyzed included body mass index (BMI), waist-to-hip ratio (WHR), waist-to-stature ratio (WSR), and a body shape index (ABSI). Models were adjusted for age, level of education, vascular risk factors, and migraine with aura. Results: After adjusting for demographics, vascular risk factors, and migraine with aura, the highest tertile of WHR was associated with CIS (OR for highest versus lowest WHR tertile 2.81, 95%CI 1.43-5.51; P=0.003). In sex-specific analyses, WHR tertiles were not associated with CIS. However, using WHO WHR cutoff values (>0.85 for women, >0.90 for men), abdominally obese women were at increased risk of CIS (OR 2.09, 95%CI 1.02-4.27; P=0.045). After adjusting for confounders, WC, BMI, WSR, or ABSI were not associated with CIS. Conclusions: Abdominal obesity measured with WHR was an independent risk factor for CIS in young adults after rigorous adjustment for concomitant risk factors.Peer reviewe

Global Outcome Assessment Life-long after stroke in young adults initiative-the GOAL initiative : study protocol and rationale of a multicentre retrospective individual patient data meta-analysis

Introduction Worldwide, 2 million patients aged 18-50 years suffer a stroke each year, and this number is increasing. Knowledge about global distribution of risk factors and aetiologies, and information about prognosis and optimal secondary prevention in young stroke patients are limited. This limits evidence-based treatment and hampers the provision of appropriate information regarding the causes of stroke, risk factors and prognosis of young stroke patients. Methods and analysis The Global Outcome Assessment Life-long after stroke in young adults (GOAL) initiative aims to perform a global individual patient data meta-analysis with existing data from young stroke cohorts worldwide. All patients aged 18-50 years with ischaemic stroke or intracerebral haemorrhage will be included. Outcomes will be the distribution of stroke aetiology and (vascular) risk factors, functional outcome after stroke, risk of recurrent vascular events and death and finally the use of secondary prevention. Subgroup analyses will be made based on age, gender, aetiology, ethnicity and climate of residence.Peer reviewe

Amnestic syndrome due to bilateral isolated sequential hippocampal infarctions: A case presentation

Transient global amnesia, acute ischemic stroke, seizures and status epilepticus, limbic encephalitis and various types of encephalopathies are included in differential diagnosis of acute-onset amnestic syndrome. Isolated hippocampal infarction is a rare cause of acute-onset amnestic syndrome. In this case presentation, we report a patient who developed permanent and severe cognitive impairment after acute-onset amnestic syndrome due to bilateral isolated hippocampal infarctions occurring nine months apart and a review of the pertaining literature is presented

Skull Base Osteomyelitis Presenting with Facial Paralysis, Low Cranial Nerve Palsies and Bilateral Carotid Involvement: A Case Report

Skull base osteomyelitis (SBO) typically presents with severe otalgia and unilateral otorrhea in immune-compromised, particularly in elderly diabetic patients. Skull base osteomyelitis usually presents with external otitis but it can also occur as a complication of acute otitis media and mastoiditis. Complications of SBO are venous sinus thrombosis, meningitis, abscess, cranial neuropathies and carotid invasion with or without ischemic stroke. Here we report a case with SBO presenting with facial paralysis, lower cranial nerve palsies and bilateral carotid involvement which occurred following sore throat and bilateral otalgia

Cerebral Venous Thrombosis in the Mediterranean Area in Adults. Role of Behcet's Disease as an Underlying Cause

Cerebral venous and dural sinus thrombosis (CVT) is a rare condition with a wide spectrum of clinical presentations. The epidemiology of the disease has evolved considerably during the recent decades with increasing oral contraceptive use in young and middle-aged women. CVT has various causes including genetic and acquired prothrombotic disorders and it usually has a favorable outcome with a low rate of thrombotic recurrence and mortality. Geographical and ethnic variations between populations may result in different distribution of CVT etiologies leading to different pathophysiological mechanisms and clinical presentations. In CVT series reported mostly from the Americas and the western European countries Behcet's disease (BD) is not reported as a common cause of CVT. However it can be discerned as a frequent cause of CVT in BD series. Due to the high prevalence of BD in the southeast Mediterranean region BD is a frequent cause of CVT in the area. Discerning characteristics of patients with BD and CVT have been reported previously and these might be helpful in guiding diagnosis and treatment of CVT especially in this part of the world