Vall d’Hebron identifies a new strategy which will help understand the causes of strokes

Ischaemic strokes are caused by a blockage in the blood vessels to the brain due to a thrombus that prevents the passage of the blood to certain areas of the brain. The origin of this thrombus is not always the same: sometimes it is an artery and on other occasions it is the heart. And for one in every three people, it is not possible to identify the cause. Now, a study headed by the Vall d’Hebron Research Institute Stroke Research Group and the Vall d’Hebron University Hospital Neurology Department’s Stroke Unit, has identified that the number of monocytes and lymphocytes in a thrombus helps distinguish its origin, which is key in beginning an optimum preventive treatment so that the patient does not suffer another stroke. The results have been published in the journal Translational Stroke Research.

The study was carried out on 178 patients at Vall d’Hebron who had suffered an ischaemic stroke who were classified according to the cause of the stroke. In 45 of them, it was confirmed that a cardioembolic stroke had occurred, meaning a thrombus originated from the heart, deriving from an atrial fibrillation, for example. In 42 of them, the cause was atherosclerosis, in other words, caused by plaque, which forms in the large arteries, such as the carotid, breaking off. Other causes were detected in nine.

It was not possible to reach a clear diagnosis for 82 patients: this is known as a cryptogenic stroke. This difficulty may be because there is a paroxysmal atrial fibrillation, a type of arrhythmia that is very complicated to detect using conventional protocols because it appears and disappears. “The detection of this cause is important to improve the monitoring of the patients. If the cause is cardiac, patients require an anticoagulant treatment to prevent the stroke from re-occurring in the future”, assures Dr Jesús Juega, assistant physician at the Vall d’Hebron University Hospital Stroke Unit and researcher for the Vall d'Hebron Research Institute Stroke Research Group.

Among the cases where the detected cause is either cardioembolic or atherosclerosis, research was made into a model of different factors that could predict the cause of the stroke. To do this, the thrombi causing the pathology were analysed. These were removed using a mechanical thrombectomy. This technique, which is performed in the most severe cases and in recent years has considerably improved the prognosis of patients, allows the flow of blood to be recovered through the brain arteries. In addition to its therapeutic use, obtaining the thrombus allows its composition to be studied using flow cytometry, a quick method which identifies the type of cells present in a sample. “We analyse the type of cells that form part of the thrombi to find possible markers relating to their origin and, therefore, the cause of the stroke”, explains Dr Jorge Pagola, assistant physician at the Vall d’Hebron University Hospital Stroke Unit and lead researcher for the Vall d'Hebron Research Institute Stroke research group.

The results of the investigation revealed a key factor in cardioembolic strokes, depending on the type of leucocytes or white blood cells present in the thrombus. On average, the thrombi originating in the heart have a higher proportion of monocytes and a lower proportion of lymphocytes. “We consider that this is an important step forward, as it is an analysis that we can perform on the patients during the hospital stage and inform the patients that they might suffer an atrial fibrillation”, explains Dr Juega. “Therefore, it is not necessary to wait weeks or months in order to check its progress”, he continues.

Relationship between monocytes and lymphocytes to discover the origin of a stroke

It was identified that the ratio of monocytes compared to lymphocytes of more than 1.6 points (in other words, having 1.6 times more monocytes than lymphocytes) indicated a higher chance of the stroke being cardioembolic in nature. As the researchers explain, the activation of the monocytes is related to the inflammation of the myocardium and it could be related to the occurrence of an atrial fibrillation.

This criterion was applied in order to classify the origins of the cryptogenic strokes, in which 66 patients had a ratio higher than 1.6 points and 16 patients had a ratio lower than 1.6 points. In order to confirm the correct classification, those suffering a cryptogenic stroke were monitored for a year to observe whether they developed any cardiac complications.

In 79% of patients with a ratio higher than 1.6 points, it was possible to confirm that the origin was effectively cardiac. Whereas for the group with a ratio of below 1.6, it was discovered that there was a cardiac cause in 31%. To improve the sensitivity and specificity of the diagnosis, this ratio can be combined with other possible predictive values, such as age or a smoking habit. “These predictive values help identify people with a higher risk of having cardiac complications and therefore informs us that we need to intensify follow-ups and perform a more thorough monitoring ”, concludes Dr. Juega.

The investigation, falling within the framework of the ITACAT project, has been carried out with the assistance of the Vall d’Hebron University Hospital Haematology, Neuroradiology and Pathological Anatomy departments and the Stroke Units at the Germans Trias i Pujol University Hospital and Bellvitge University Hospital. The project has been made possible thanks to the funding received from La Marató charity event organised by the local Catalan television station TV3.