Between 15–20% of cases of brain infarction involve patients under the age of 55 years—that is, 150 000 to 200 000 patients each year in Europe. The main causes include cardiac valve disease and dissections of extracranial arteries (accounting for up to 20% of cases). In this age range, rare causes of arteriopathies may be found more frequently than in older stroke patients. Their mechanism is either inflammatory disease, infectious, metabolic, or toxic. Atherosclerosis accounts for 10% of cases. Over 150 causes of stroke have been listed. However, despite a thorough evaluation, the cause of the stroke remains unknown in up to 50–60% of cases in patients younger than 55 years.

In this group, transoesophageal echocardiography (TOE) shows inter-atrial septal abnormalities in 55–60% of cases. The same abnormal septum is observed in 20% of the normal population. However, when present in a patient with a stroke of unknown cause, is this abnormality responsible for the stroke or the marker for the true cause of stroke? For example, having yellow nails is statistically associated with lung cancer, but does not mean that yellow nails cause lung cancer.

PFO AND STROKE: A STATISTICAL ASSOCIATION

In 1988, Lechat and colleagues¹ performed transthoracic echocardiography (TTE) with contrast micro-bubble injection and showed that patients with stroke of unknown cause more frequently had PFOs than controls. Since then, numerous studies concurred with this result and have been summarised in a meta-analysis (fig 1).²

In a study using TOE in 100 patients and 55 controls younger than 55 years, we found that a PFO was present in 43% of patients, 56% of patients with brain infarction of unknown cause, and in only 18% of controls (odds ratio (OR) 3.9, 95% confidence interval (CI) 1.5 to …