Etiologic workup in cases of cryptogenic stroke: a systematic review of 1 international clinical practice guidelines

Mcmahon, Naoimh orcid iconORCID: 0000-0001-6319-2263, Bangee, Munirah orcid iconORCID: 0000-0001-8548-6692, Benedetto, Valerio orcid iconORCID: 0000-0002-4683-0777, Bray, Emma orcid iconORCID: 0000-0001-9882-3539, Georgiou, Rachel, Gibson, Josephine orcid iconORCID: 0000-0002-3051-1237, Lane, Deirdre A., Al-Khalidi, A. Hakam, Chatterjee, Kausik et al (2020) Etiologic workup in cases of cryptogenic stroke: a systematic review of 1 international clinical practice guidelines. Stroke, 51 (5). ISSN 0039-2499

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Background and purpose
Identifying the etiology of acute ischemic stroke is essential for effective secondary prevention. However, in at least one third of ischemic strokes, existing investigative protocols fail to determine the underlying cause. Establishing etiology is complicated by variation in clinical practice, often reflecting preferences of treating clinicians and variable availability of investigative techniques. In this review, we systematically assess the extent to which there exists consensus, disagreement, and gaps in clinical practice recommendations on etiologic workup in acute ischemic stroke.
We identified clinical practice guidelines (CPGs)/consensus statements through searches of four electronic databases, and hand-searching of websites/reference lists. Two reviewers independently assessed reports for eligibility. We extracted data on report characteristics and recommendations relating to etiologic workup in acute ischemic stroke, and in cases of cryptogenic stroke. Quality was assessed using the AGREE II tool (Appraisal of Guidelines for Research & Evaluation). Recommendations were synthesised according to a published algorithm for diagnostic evaluation in cryptogenic stroke.
We retrieved sixteen CPGs and seven consensus statements addressing acute stroke management (n=12), atrial fibrillation (n=5), imaging (n=5), and secondary prevention (n=1). Five reports were of overall high quality. For all patients, guidelines recommended routine brain imaging, non-invasive vascular imaging, a 12-lead electrocardiogram (ECG), and routine blood tests/laboratory investigations. Additionally, ECG monitoring (>24 hours) was recommended for patients with suspected embolic stroke, and echocardiography for patients with suspected cardiac source. Three reports recommended investigations for rarer causes of stroke. None of the reports provided guidance on the extent of investigation needed prior to classifying a stroke as ‘cryptogenic’.
While consensus exists surrounding ‘standard’ etiologic workup, there is little agreement on more advanced investigations for rarer causes of acute ischemic stroke. This gap in guidance, and in the underpinning evidence, demonstrates missed opportunities to better understand and protect against ongoing stroke risk.

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