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ObjectiveCardiac diseases are established risk factors for ischemic stroke incidence and severity. Conversely, there is increasing evidence that brain ischemia can cause cardiac dysfunction. The mechanisms underlying this neurogenic heart disease are incompletely understood. Although it is established that ischemic stroke is associated with cardiac arrhythmias, myocardial damage, elevated cardiac enzymes, and plasma catecholamines in the acute phase, nothing is known about the delayed consequences of ischemic stroke on cardiovascular function.MethodsTo determine the long‐term cardiac consequences of a focal cerebral ischemia, we subjected young and aged mice to a 30‐minute transient middle cerebral artery occlusion and analyzed cardiac function by serial transthoracic echocardiography and hemodynamic measurements up to week 8 after surgery. Finally, animals were treated with metoprolol to evaluate a pharmacologic treatment option to prevent the development of heart failure.ResultsFocal cerebral ischemia induced a long‐term cardiac dysfunction with a reduction in left ventricular ejection fraction and an increase in left ventricular volumes; this development was associated with higher peripheral sympathetic activity. Metoprolol treatment prevented the development of chronic cardiac dysfunction by decelerating extracellular cardiac remodeling and inhibiting sympathetic signaling relevant to chronic autonomic dysfunction.InterpretationFocal cerebral ischemia in mice leads to the development of chronic systolic dysfunction driven by increased sympathetic activity. If these results can be confirmed in a clinical setting, treating physicians should be attentive to clinical signs of heart failure in every patient after ischemic stroke. Therapeutically, the successful β‐blockade with metoprolol in mice could also have future clinical implications. Ann Neurol 2017;82:729–743

rv TOMAS ISAKOWITZ, MICHAEL BIEBER, AND FABIO VITALI, GUEST EDITORST hree years ago, when two of us guest edited a special section on hypermedia design for this magazine [l], the Web was a relatively nascent field. At that time, our focus was on the general principles for designing hypermedia applications. Since then, the scope of Web-based applications has grown enormously, now encompassing four general kinds of Web-based systems: Intranets^ to support internal work, Web-presence sites that are marketing tools designed to reach consumers outside the firm, electronic commerce systems that support consumer interaction, such as online shopping, and a blend of internal and external systems to support business-tobusiness communication, commonly called extranets. Thus, a Web platform has transformed itself in the 78 ]iilx 1998/Vol 41, No 7 COMMUNICATIONS OF THE ACM This spctwl secrion was suppontd liy tht NASA

Background and Purpose— The selection of appropriate neurological scores and tests is crucial for the evaluation of stroke consequences. The validity and reliability of neurological deficit scores and tests has repeatedly been questioned in ischemic stroke models in the past. Methods— In 198 male mice exposed to transient intraluminal middle cerebral artery occlusion, we examined the validity and reliability of 11 neurological scores (Bederson score 0–3, Bederson score 0–4, Bederson score 0–5, modified neurological severity [0–14], subjective overall impression [0–10], or simple neurological tests: grip test, latency to move body length test, pole test, wire hanging test, negative geotaxis test, and elevated body swing test) in the acute stroke phase, that is, after 24 hours. Combinations of neurological scores or tests for predicting infarct volume were statistically analyzed. Results— Infarct volume was left skewed (median [Q1–Q3], 78.4 [54.8–101.3] mm 3 ). Among all tests, the Bederson (0–5; r=0.63, P <0.001), modified neurological severity (r=0.80, P <0.001), and subjective overall impression (r=−0.63, P <0.001) scores had the highest test validities, using infarct volume as external reference. Subjective overall impression had the best agreement between 5 raters (Kendall W=0.11, P <0.001). The Bederson (0–5) score discriminated infarct volume in mice with small (≤50 mm 3 ; r=0.33, P =0.027) and large (>50 mm 3 ; r=0.48, P <0.001) brain infarcts, all other tests only in mice with large infarcts. Combining subjective overall impression with Bederson (0–5) score explained 47.6% of the variance of infarct volume. Conclusions— Despite their simplicity, the Bederson (0–5) score, modified neurological severity score, and subjective overall impression have reasonable validity and reliability in the acute stroke phase. The Bederson (0–5) score equally distinguishes infarct volume in small and large infarcts. Visual Overview— An online visual overview is available for this article.