Heart and Blood Diseases

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Natriuretic Peptide, Brain

N,N-dimethylarginine

Enzyme Inhibitors

Patients with stroke of undetermined cause age 18-65

ADMA, NTproBNP, IL-6, Adiponectina, Leptine, Syndecan, Resistin

ADMA (asymmetric dimethylarginine) , NTproBNP (N-terminal pro b-type natriuretic peptide), IL-6 (Interleukin 6), Adiponectina, Leptine, Syndecan, Resistin

A stroke is the second cause of deaths after heart attack, one of the most important causes of malfunction as far as adults are concerned and the second as for the frequency cause of dementia. In spite of a possibility of the therapy of stroke ( tissue plasminogen activator) and recognized most of risk factors there is expected that incidence rate on stroke connected with ageing of the society will be growing. It will cause medical and social consequences.

There are many of potential causes of cardiac strokes, which are not entirely examined.

More over many cryptogenic strokes are presumed to have an embolic etiology, and the frequent cause of these kind of strokes at young age is probably the mechanism of paradoxical embolism through patent foramen ovale.

As far as the investigators are concerned, at present there is lack of any recommendations for these scientific hypothesis.

A stroke is the second cause of deaths after heart attack, one of the most important causes of malfunction as far as adults are concerned and the second as for the frequency cause of dementia. In spite of a possibility of the therapy of stroke ( tissue plasminogen activator) and recognized most of risk factors there is expected that incidence rate on stroke connected with ageing of the society will be growing. It will cause medical and social consequences.

The risk factors of stroke can be divided into alterable and not alterable. Importantly, the not alterable factors are: age, sex, race and genetic factors. After the age of 55 the risk of stroke grows twice in every decade of life. Moreover, it was alleged that incidence rate on stroke is more frequent at women than at men. At the black race the incidence rate on stroke is twice more frequent than at white race.

Well- known are also genetic syndromes connected with strokes like s. MELAS or CADASIL.

Well- known alterable factors are:

* hypertension
* coronary disease
* atrial fibrillation
* hypercholesterolemia
* diabetes
* nicotinism
* blood clotting disorder
* alcoholism
* TIA (transient ischemic attack) or previous former stroke
* asymptomatic stenosis of internal carotid artery

Cardiogenic stroke is a stroke caused by embolic material, which was created in cardiac cavities or on cardiac valves. They comprised 11% of all strokes and 25% of ischemic strokes. Additionally, among patients over 80 years old cardiac causes are responsible for even 40% of all ischemic strokes and half of cardiogenic strokes is caused of atrial fibrillation. Among young people (below 45 years old) about 50% of strokes are cardiogenic and are connected with paradoxical embolism at patients with patent foramen ovale.

Furthermore, cardiac- brain embolism is a result of:

* structural defect of cavities and valves of heart
* arrhythmia
* disturbances of movability of walls of the heart and function of endocardium which leads to increased risk of the risk of parietal thrombus
* cardiac insufficiency

There are many of potential causes of cardiac strokes, which are not entirely examined as for example:

* small pockets of intra- atrial septum
* structures in dextral atrium like Eustachian valve or Chiari network
* there is also a theory that even enlargement of left atrium may be the cause of brain stroke
* aneurysm of intra- atrial septum.

As far as the investigators are concerned, at present there is lack of any recommendations for these scientific hypothesis.

Available data suggest that in the comparison with atherosclerosis and lacunar strokes cardiogenic strokes characterize with high mortality ranging of 27%. Also the risk of relapse is higher than in strokes of other etiology.

Nevertheless, unfortunately, in spite of wide diagnostics at about 25-30% of patients with ischemic stroke the cause is unknown. This kind of stroke is called cryptogenic stroke or stroke with undefined etiology.

They constitute almost half of all ischemic stroke at young patients (below 55 years old). Many cryptogenic strokes are presumed to have an embolic etiology, and the frequent cause of these kind of strokes at young age is probably the mechanism of paradoxical embolism through patent foramen ovale.

To conclude, currently there aren't researches defining recommendations for long- lasting treatment patients with rare causes of strokes.

Biomarkers, Hemodynamic and Echocardiographic Predictors of Ischemic Strokes and Their Influence on the Course and Prognosis

NTproB (N-terminal pro b-type natriuretic peptide)

Medical University of Lodz

Principal Investigator

Blood and Lymph Conditions

Hemostatic Disorders

Blood Coagulation Disorders

Coagulants

Fibrin fragment D

Acute ischemic stroke patients at high-risk for underlying occult cancer (elevated D-dimer and suspicion of ESUS at admission)

Simon Jung, MD

Morin Beyeler, MD

Michel Patrik

Davide Strambo

Mira Katan, MD

Johannes Frenger

INVISIBLE-1 aims to prospectively follow patients up to one year after ischemic stroke to:

1. Determine the cumulative incidence of occult cancer in patients with embolic stroke of undetermined source (ESUS) and elevated D-dimer
2. Describe occult cancer characteristics and spontaneous course of occult cancer

Methodology

The investigators will include 370 stroke patients with elevated D-dimer (≥ 820 μg/L) at the time of stroke, suspicion of ESUS after initial workup and without known cancer. The investigators will perform a follow-up telephone interview at one year to assess the occurrence of a new cancer and characterize the course of the disease.

Significance

Determining the real incidence of occult cancer in high-risk patients will help support the implementation of screening trials in the future. Faster detection and treatment of occult cancers would significantly impact patient' outcomes by offering faster cancer treatment and optimal secondary stroke prevention.

INVISIBLE-1 is the first prospective study conducting a 1-year post-stroke follow-up telephone interview in preselected stroke patients at high-risk for occult cancer.

INVISIBLE-1 aims to:

1. Prospectively determine the cumulative incidence of occult cancer in patients with elevated D-dimer and ESUS within 1 year after the ischemic stroke
2. Describe occult cancer characteristics and spontaneous course of occult cancer

Hypothesis

Elevated D-dimer and suspicion of ESUS at admission may predict an underlying unknown cancer at the time of index stroke. The investigators hypothesize that the cumulative incidence of newly diagnosed cancer within 1 year after stroke reaches 15% in patients presenting these characteristics. This percentage is higher than the 10% currently known according to available retrospective studies.

Project design

To ensure the recruitment of the majority of potential occult cancer patients, the investigators set the D-dimer cut-off for inclusion of ≥ 820 μg/L at admission, based on our intern retrospective analyses of 1001 patients (OCCULT-5 score). In patients with ESUS, this cut-off was associated with a sensitivity of 91% and a specificity of 56% for the presence of an occult cancer diagnosed within 1 year after the index-stroke.

As suggested by the current evidence, the investigators decided to set the limit for diagnosis of new cancer at 1 year after the index stroke. Beyond this period, the causality is questionable in our opinion.

Discovery of New Cancer in the 1-year Follow-up After Ischemic Stroke in Patients at Risk: The INVISIBLE-1 Study

The description of the specific characteristics of occult cancers is defined by the location of the cancer, the histological type of cancer, the date of suspicion of cancer (e.g. via imaging), the type of investigation leading to the suspicion of cancer, the date of final diagnosis via histology, the presence of metastases at diagnosis, the type of treatment provided and the date of start of treatment.

The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability. The higher the mRS score, the more disabled or dependent the patient (mRS 6 represents death).

NIHSS is used to quantify stroke severity. It ranges from 0 to a maximum of 42 points. The higher the score, the more extensive the stroke.

Insel Gruppe AG, University Hospital Bern

Dept. of Neurology, Inselspital Bern

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Biomarkers, Hemodynamic and Echocardiographic Predictors of Ischemic Strokes and Their Influence on the Course and Prognosis	NCT03377465	Embolic Stroke ... Ischemic Stroke Atrial Fibrilla... Myocardial Infa... Cardiac Tumor Endocarditis Patent Foramen ...	ADMA (asymmetri...	18 Years - 65 Years	Medical University of Lodz
Discovery of New Cancer in the 1-year Follow-up After Ischemic Stroke in Patients at Risk: The INVISIBLE-1 Study	NCT06100718	Cancer-related ... Paraneoplastic ... Occult Cancer Ischemic Stroke Embolic Stroke ... D-dimer		18 Years -	Insel Gruppe AG, University Hospital Bern
Biomarkers, Hemodynamic and Echocardiographic Predictors of Ischemic Strokes and Their Influence on the Course and Prognosis	NCT03377465	Embolic Stroke ... Ischemic Stroke Atrial Fibrilla... Myocardial Infa... Cardiac Tumor Endocarditis Patent Foramen ...	ADMA (asymmetri...	18 Years - 65 Years	Medical University of Lodz

Spots Global Cancer Trial Database for embolic stroke of undetermined source