Prime time for dissecting the entity of cryptogenic stroke.

T he term cryptogenic ischemic stroke (or stroke of unde-termined pathogenesis) encompasses ischemic strokes without specific cause detected after adequate diagnostic workup. Cryptogenic stroke is, thus, a diagnosis done by exclusion. Strokes may remain cryptogenic if diagnostic evaluation is incomplete for one or another reason or in the presence of multiple competitive causes, such as atrial fibril-lation (AF) and atherosclerotic stenosis in an ipsilateral relevant artery. Choosing the particular diagnostic investigation should always be balanced between the cost and potential yield, considering patient characteristics and the effect on treatment decisions. The only patients with stroke in whom thorough pathogenic workup may be unnecessary are those whose poor prognosis cannot be improved reasonably by pathogenic diagnosis. A substantial proportion of all strokes end up being cryp-togenic. Among the 5017 patients in the German Stroke Data Bank, cryptogenic strokes accounted for 23%. 1 Notably, the cryptogenic category is even larger among younger patients reflecting major challenges in defining their pathogenesis and interpreting causally relevant findings. A total of 40% of patients aged <50 years remained without elusive cause for their stroke in a recent large multicenter survey. 2 Furthermore, another prospective study with MR-imaged patients aged <55 years showed higher rates of cryptogenic strokes with lower age. 3 There is paucity of data to guide secondary prevention after cryptogenic stroke. Current guidelines either did not give statements specifically on cryptogenic stroke or recommended antiplatelet therapy. 4,5 Anticoagulation (warfarin with target international normalized ratio, 1.4–2.8) has been compared against aspirin (325 mg/d) only in 1 randomized trial subgroup of cryptogenic stroke (n=576), with no difference in the primary outcome of ischemic stroke or death >2 years (15.0% versus 16.5%). 6 About patent foramen ovale, a prevalent feature in both general population and in younger patients with cryptogenic stroke, warfarin was not superior to aspirin, 7 and patent foramen ovale closure in unselected patients with unselected device was not beneficial compared with the best medical treatment to reduce the risk of recurrent strokes in the recently completed randomized trials. 8 Amid these limited data on secondary prevention, clinical and subclinical recurrence risk after cryptogenic stroke remains significant. A South Korean study showed a very high rate (30%) of recurrent stroke after cryptogenic stroke in a relatively short 1-year follow-up. 9 Furthermore, another recent study found a 14.5% rate of new silent ischemic MRI lesions at 90-day follow-up although 1.2% had a clinical recurrent stroke …