Stroke can be the initial manifestation of a host of systemic conditions that either are treatable by themselves or must be identified to avoid misdi- rected ineffective or harmful therapies. The pretest probability of finding a diagnostically meaningful abnormality for many of these tests will depend on clinical suspicion informed by demographic variables (eg, age), medical history, physical find- ings, and results of basic testing. For example, the yield of testing for a hypercoagulable state is low for patients >50 years of age.90 Patients present- ing with stroke will have echocardiographically con- firmed infectious endocarditis in 1.7% of cases, and an initial C-reactive protein of at least 10 mg/L dramatically increased the likelihood of infectious endocarditis (odds ratio [OR], 22).70 Use of cocaine within the prior 24 hours increases the risk of stroke in young adults by >6-fold.71 Toxicology testing for cocaine and other drugs of abuse should be done at the time of presentation.91,92 When diagnostic algo- rithms were used, monogenic causes of stroke were 11. Identification of symptomatic intracranial athero- sclerotic disease supports treatment to aggressive antiatherosclerotic targets and is often seen as an indication for dual antiplatelet therapy (DAPT). have been shown to reli- ably exclude high-grade intracranial atherosclerotic stenosis (ICAS) when digital subtraction catheter angiography was used as the reference test. Early identification of symptomatic extracranial vertebro- basilar stenosis identifies patients at high risk of 12. Hemorrhagic transformation is often seen as a con- traindication to early (<2 weeks of stroke onset) oral anticoagulation, although no randomized trial has been done that directly addresses the question. 