Response to Letter by Altieri et al
We thank Altieri and colleagues for their response letter and for their insightful comments regarding our novel article.
The core message that pervades our manuscript is that May-Thurner syndrome potentially represents a novel risk factor for embolic stroke. The diagnosis of May-Thurner syndrome in a patient who had sustained a stroke of cryptogenic etiology, as a sole entity, likely does not increase the risk of embolic stroke. However, in association with other concomitant risk factors such as a thrombophilic disorder, birth control pills and a patent foramen ovale (PFO), then May-Thurner syndrome can potentially lead to a higher risk of embolic stroke. It must be also pointed out that in the context of embolic stroke, not all thrombophilic conditions warrant lifelong anticoagulation and some patients may be genetically resistant to antiplatelet therapy.1 The benefits of PFO closure in these patients outweigh the associated risks of the procedure, which are low, approximately 2.2% when performed in centers of excellence.2 Because the risk of stroke in the general population is estimated to be ≈1% per year, and PFO is an independent risk factor for stroke,3 a therapeutic intervention to lower this risk appears justified, particularly given that the current best alternative strategy of initiating permanent oral anticoagulation is not only cumbersome but carries a substantial risk for bleeding.
We agree with the authors that the current definition of “cryptogenic stroke” can indeed be “cryptic” and often times reflects the lack of an exhaustive, comprehensive work-up to determine etiology. Mohr and colleagues reported in a 1978 registry data from 215 patients with acute stroke caused by cerebral embolism.4 In 37% of these embolic strokes, no identifiable cardiac embolic source was found. These cases represent the first reported “infarcts of undetermined cause.” The terminology “cryptogenic stroke” was not used in the literature until 1988.5 The phrase failed to achieve adoption of a ubiquitous status, and Sacco et al reported a series of 508 cases that were labeled as infarcts of undetermined cause, of which 138 (27%) were evaluated with both computed tomography and angiography.6 The TOAST classification of stroke of undetermined etiology states that “some patients will have no likely etiology determined despite an extensive evaluation. In others, no cause is found but the evaluation was cursory. This category also includes patients with two or more potential causes of stroke so that the physician is unable to make a final diagnosis.”7 This definition of “cryptogenic stroke” is not applicable to patients described in our article.
We conclude that the presence of May-Thurner syndrome along with a PFO in association with other risk factors potentiates the risk of embolic stroke. Our personal opinion is that individualized treatment using PFO closure together with optimal medical therapy offers benefit to patients with MTS.
The term “cryptogenic stroke” is a historical oxymoron, and in this period of rapidly developing technology, is ever evolving; perhaps we have reached an époque where the terminology needs to be redefined to clarify what constitutes a cryptogenic stroke and what does not.
“O body swayed to music, O brightening glance, how can we know the dancer from the dance?” —W. B. Yeats
Mohr JP, Caplan LR, Melski JW, Goldstein RJ, Duncan GW, Kistler JP, Pessin MS, Bleich HL. The Harvard Cooperative Stroke Registry: a prospective registry. Neurology. 1978; 28: 754–762.
Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE III. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. TOAST–Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993; 24: 35–41.