Etiologic Workup in Cases of Cryptogenic Stroke

Abstract

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. Methods— We identified clinical practice guidelines/consensus statements through searches of 4 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 synthesized according to a published algorithm for diagnostic evaluation in cryptogenic stroke. Results— We retrieved 16 clinical practice guidelines and 7 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, noninvasive vascular imaging, a 12-lead 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 before classifying a stroke as cryptogenic. Conclusions— 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. Registration— URL: https://www.crd.york.ac.uk/PROSPERO/ ; Unique identifier: CRD42019127822.

Machine Learning Analysis of the Cerebrovascular Thrombi Proteome in Human Ischemic Stroke: An Exploratory Study

“…Use of intravenous thrombolysis (IVT) treatment was allowed and administrated according to current guidelines (10). Stroke cause was defined by a stroke neurologist blinded to the proteomics analysis, according to the TOAST (Trial of ORG 10172 in Acute Stroke Treatment) (14) classification, after an exhaustive in-hospital workup (15) including at least computed tomography and magnetic resonance imaging, duplex sonography of the cervical arteries, blood coagulation tests, long-term electrocardiography, and transthoracic or transesophageal echocardiography. Stroke etiology was defined as "atherothrombotic tandem" when CT angiography and MR angiography demonstrated >50% stenosis or occlusion of the cervical carotid artery with associated intracranial ICA or MCA occlusion ipsilateral to the symptomatic hemisphere, in addition to exclusion of potential sources of cardiac embolism.…”

Transesophageal echocardiogram in the evaluation of acute ischemic stroke of young adults

“…There is no universally accepted diagnostic work protocol due to limitation of data on cost-effectiveness and diagnostic yield of different tests. [ 22 32 33 ] There is also heterogeneity in the results of the previously published data with the diagnostic tests used for the detection of cardiac sources of embolism rating 20%–47%. The underlying mechanism of AIS in young adults remains unknown after the RDW in at least 35% of the patients in our center.…”

Cryptogenic Stroke: Cardiac Rhythm Monitoring as An Indispensable Screening Modality

“…Patent foramen ovale, PAF, aortic arch atherosclerosis, substenotic atherosclerosis, atrial cardiopathy, and LAA dysfunction are several possible pathophysiologies implicated in cryptogenic stroke. 6 A systematic review by McMahon et al 7 recommended several diagnostic modalities to investigate the cause of cryptogenic stroke, including brain imaging with non-contrast CT scan and MRI, vascular imaging with Coronary Computed Tomography Angiography (CCTA), magnetic resonance angiography (MRA), or Doppler ultrasound, laboratory tests, cardiac imaging, and cardiac monitoring.…”