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Test tubes in a lab

Doctoral defence of Juha Onatsu, Lic Med, 1 Oct 2021: New biomarkers may improve stroke diagnostics and prognostics

The doctoral dissertation in the field of Neurology will be examined at the Faculty of Health Sciences at Kuopio Campus.

The doctoral dissertation of Juha Onatsu assesses the use of inflammatory, neuro-axonal and imaging biomarkers in stroke patients.

Stroke is responsible for 10% of all global deaths and is the second leading cause of death and the third leading cause of disability. Ischemic stroke accounts about 80% of all events and an embolism of cardiac origins is the cause of about every fifth of these occurrences. Atrial fibrillation is the most common cause of brain embolism, but there are many other structural changes in the heart, that can predispose to  the formation of  thrombi. Despite a thorough etiological work-up, the reason behind the stroke remains unknown in 25% to 40% of cases - these are called cryptogenic strokes.

Non-contrast computed tomography (NCCT) is the basic imaging method applied in patients with acute stroke since it can rule out or confirm the presence of an intracranial hemorrhage and furthermore, the early signs of ischemia or hints of large vessel occlusion may be seen.

Contrast enhanced CT can be used to diagnose carotid artery stenosis and dissection and recently also cardiac sources of emboli. Until now, echocardiography has been the golden standard to permit the identification of a possible cardiac source of the embolism. The prediction of outcome after ischemic stroke is mainly based on the patient’s age, stroke severity and premorbid disability. However, blood biomarkers reflecting different pathophysiological processes in acute stroke may supplement the performance of these models.

The researchers investigated if a composite examination of the heart, aorta and cervicocranial arteries with computed tomography (CACC-CT) could improve the etiologic evaluation in patients with a suspected stroke of cardiogenic origin. They also evaluated if inflammatory mechanisms were involved in stroke etiology and outcome. Additionally they studied if neuro-axonal proteins in blood are related to the outcome and diagnosis of stroke or TIA.

It was observed that CACC-CT and transthoracic or transesophageal echocardiography (TTE/TEE)  together were more sensitive than TTE/TEE alone for detecting cardiac or aortic high-risk findings for embolism. TTE/TEE was inferior to CACC-CT in visualizing myocardial infarction with left ventricular aneurysm. In contrast, CACC-CT was not suitable for detecting small left atrial thrombi, a patent foramen ovale or for measuring the ejection fraction of the left ventricle.

Soluble urokinase-type plasminogen activator receptor (suPAR) concentrations were found to be higher in those patients who suffered a stroke/transient ischemic attack due to large artery atherosclerosis as compared to small vessel disease. Additionally, an elevated plasma suPAR concentration was associated with all-cause mortality during the five year follow-up.

Serum levels of neurofilament light chain and serum Tau concentrations were higher in patients with  acute ischemic stroke (AIS) than in those with TIA and the serum levels correlated with the stroke volume and functional outcome after three months.

The results suggest that CACC-CT can add value to TTE/TEE in the etiological diagnostics of cryptogenic stroke and furthermore that neuroaxonal biomarkers may assist in both stroke diagnostics and in the prognostification of the outcome after a stroke.

The doctoral dissertation of Juha Onatsu, Licentiate of Medicine, will be examined at the Faculty of Health Sciences. The Opponent in the public examination will be Docent Tiina Sairanen of the University of Helsinki, and the Custos will be Professor Pekka Jäkälä of the University of Eastern Finland. The public examination will be held online in Finnish on 1 October 2012, starting at 12 noon.

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Public examination