Background. The significance of the Hyperdense Middle Cerebral Artery Sign (HMCAS) is uncertain. Aims. This prospective study investigated the sensitivity, specificity, prevalence, prognosis, interobserver variability, and associated clinical features of HMCAS in acute ischemic stroke. Methods. Initial CT scans of 117 patients with acute ischemic stroke or transient ischemic attack (TIA) and 65 age-matched controls were reported independently by two neuroradiologists blinded to diagnosis. Details of initial stroke severity and comorbidities were collected, and outcome on the modified Rankin scale (mRS) was assessed at 3–6 months. Results. HMCAS was seen in 15% of all ischemic strokes and 25% of all middle cerebral artery (MCA) strokes; specificity was 100%. HMCAS was associated with more severe initial deficit and atrial fibrillation. Only 21% of patients with a first-ever MCA stroke and HMCAS had a good outcome ( ) compared to 55% of those without the sign ( ). Interobserver agreement was only 0.747 (Kappa statistic). Conclusion. The prevalence, specificity, sensitivity, and clinical associations of HMCAS were similar to previous reports. This study confirmed prospectively that HMCAS was associated with a poorer outcome at 3 to 6 months and demonstrated interobserver variability in detection of the sign. 1. Introduction The Hyperdense Middle Cerebral Artery Sign (HMCAS) was first described about thirty years ago as a high-density structure within the territory of the middle cerebral artery (MCA) on nonenhanced Computed Tomography (NECT) scans of patients with acute ischemic stroke [1]. A number of investigators have calculated the sensitivity and specificity of the HMCAS, as well as the relationship between the presence of the sign and initial stroke severity [2–6]. Collectively, the published data suggest the sign is highly specific and associated with a more severe initial deficit [7–9]. Associations between the HMCAS and risk factors for ischemic heart disease, hypercoagulopathy, and atrial fibrillation (AF) have also been described [10, 11]. Research has focused predominantly on the prognostic implications in patients who demonstrate an HMCAS on early NECT scans [12–16]. The consensus is that the presence of an HMCAS is associated with a poorer outcome. However, the majority of studies looking at this have been retrospective. There are no published studies that have looked prospectively at the natural history of patients with an HMCAS, that is, without thrombolysis, beyond twenty-one days. Recent studies have evaluated the outcome of thrombolytic
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