You can't let your doctor get by with not figuring out THE EXACT REASON FOR YOUR STROKE. Damned difficult to prevent the next one if your doctor fails at finding the reason.
Stroke Prevention After Cryptogenic Stroke
Current Cardiology Reports volume 23, Article number: 174 (2021)
Abstract
Purpose of Review
Cryptogenic stroke represents a heterogenous but clinically important collection of stroke etiologies for which our understanding continues to grow. Here, we review our current knowledge and most recent recommendations on secondary prevention for common causes of cryptogenic stroke including paroxysmal atrial fibrillation, atrial cardiopathy, patent foramen ovale, and substenotic atherosclerotic disease as well as the under-recognized mechanisms of occult malignancy, heart failure, and, most recently, infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).
Recent Findings
The results from recent observational studies and randomized clinical trials have provided greater insight into the causal relationship and attributable risk of these suspected etiologies and have identified potential strategies to reduce the rates of recurrence. However, further clinical trials are needed to confirm the benefits of specific stroke prevention strategies, including the patient populations most likely to benefit from anticoagulation.
Summary
There is ongoing research aimed at both reducing the proportion of ischemic strokes classified as cryptogenic and resolving much of the clinical equipoise that still exists. The results of these studies have the potential to provide us with a better understanding of these occult mechanisms and allow for more targeted interventions.
Introduction
Ischemic strokes can result from several different mechanisms, the majority of which can be readily identified following a standard diagnostic evaluation. However, in about 25% of cases stroke etiology remains unknown—a clinically important point as the effectiveness of secondary prevention strategies often hinges on accurate and timely identification of the underlying cause [1]. Our understanding of cryptogenic stroke has evolved through the years and depends on the classification system used. An early and commonly used system arose from the TOAST (Trial of Org 10,172 in Acute Stroke Treatment) study which classified ischemic strokes based on five potential etiologies: [1] large artery atherosclerosis, [2] cardioembolism, [3] small vessel occlusion, [4] other determined etiology (e.g., dissection), or [5] of undetermined source (i.e., cryptogenic) [2]. According to the TOAST system, strokes could be classified as cryptogenic [1] after an extensive evaluation, [2] after an incomplete evaluation, or [3] due to the presence of multiple competing etiologies. The simplicity of the system has made it widely popular for use in both clinical practice and scientific research. However, through the years, as stroke research has evolved (along with our standards for optimal care), TOAST’s broad inclusion criteria for cryptogenic stroke has complicated efforts towards targeted medical management. Since then additional classification systems have been developed, emphasizing underlying mechanisms (causative) and/or disease manifestations (phenotypic) (Table 1) [2,3,4]. In an attempt to identify a single and therapeutically distinct subset of patients with cryptogenic stroke, Hart and colleagues proposed the concept of ESUS, or embolic stroke of undetermined source, broadly defined as nonlacunar brain infarcts occurring in the absence of [1] ≥ 50% luminal atherosclerotic stenosis of the supplying extracranial or intracranial arteries, [2] any major-risk cardioembolic source, and [3] any other specific cause of stroke (e.g., dissection, vasospasm, drug abuse) [5]. With this distinction, the authors proposed there was likely a subset of cryptogenic strokes that were more likely embolic in origin and perhaps more likely to respond to anticoagulant therapy. However, even with these new constructs, cryptogenic stroke remains a diagnostic challenge. As the 10-year risk of recurrence is estimated to be as high as 30%, investigations into potential sources of cryptogenic stroke should be focused and deliberate—guided by patient factors and clinical features aimed at increasing the yield of diagnostic studies and identifying patients who would likely benefit from targeted therapies [6].
In the last 5 years, several clinical trials have investigated the efficacy of newer therapies for specific conditions often implicated in cryptogenic stroke. Non-vitamin K oral antagonists (NOACs), such as dabigatran, rivaroxaban, and apixaban have been explored in patients with ESUS, heart failure, and malignancy with varying degrees of success [7, 8••, 9•]. The results of these studies have inspired additional trials using these new agents in more select sub-populations. In addition, the recent CLOSE, REDUCE, and DEFENSE-PFO studies identified patients with cryptogenic stroke and PFO who may benefit most from PFO closure, prompting a recent update in the recommendations from the American Academy of Neurology [10,11,12]. Although these discoveries highlight recent progress in the area of cryptogenic stroke, their gaps and limitations emphasize the need for continued work into interventions that may further reduce the risk of recurrence in these special populations.
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