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Source: Manelfe C, et al. Association of hyperdense middle cerebral artery sign with clinical outcome in patients treated with tissue plasminogen activator. Stroke 1999;30:769-772.
A hyperdense middle cerebral artery (MCA) on CT scan was first identified as a marker of thrombus in the MCA in 1983 (Gacs G, et al. Stroke 1983;14:756-762). Although the hyperdense MCA sign has a high specificity for MCA occlusion, its sensitivity is low, and false positive signs, usually bilateral, have been noted in patients with calcific atherosclerotic cerebrovascular disease or a high hematocrit (Tomsick TA, et al. Neuroradiology 1989;31:312-315). Previous studies have associated the hyperdense MCA sign with severe neurological deficit and poor clinical outcome, but the number of patients has been small (Moulin T, et al. Neurology 1996;47:366-375).
The present study was aimed at determining the frequency of the hyperdense MCA sign, its association with stroke severity and early ischemic changes on CT, its relevance to clinical outcome, and the efficacy of intravenous (IV) recombinant tissue plasminogen activator (rtPA) in stroke patients with this radiologic sign.
Manelfe and colleagues analyzed data from more than 600 patients who received either rtPA or placebo in the ECASS I trial (Hacke W, et al. JAMA 1995;274:1017-1025). CT scans were obtained within six hours from onset of symptoms. Functional outcomes were assessed at day 90 using the modified Rankin and Scandinavian Stroke Scales. A high-density MCA sign was noted in 107 out of 603 patients (18%) on the baseline CT. This sign of MCA thrombus persisted in 56 of 106 patients (55%) on a subsequent CT on day 1, but in only 22 of 86 patients (26%) on a CT scan at one week.
Patients with a high-density MCA sign had a more severe neurological deficit (P < 0.0001) and more commonly had cerebral edema or mass effect on the baseline CT (P < 0.0001). This sign of MCA thrombus on the baseline CT was significantly associated with a poor clinical outcome at day 90 on univariate analysis: 84% of patients with a high-density MCA were dependent or dead at that time compared with only 62% of patients without the sign (P < 0.0001). Nevertheless, the high-density MCA sign had no independent prognostic value in a logistical model that took into account among others: age, initial severity of the neurological deficit, and changes on the baseline CT scan.
Among the 107 patients with a high-density MCA sign, 46 patients who received rtPA had a better neurological recovery than the 61 who received placebo (P = 0.03). Mortality at day 90 was not significantly greater in the rtPA group.
This analysis of ECASS I patients with a hyperdense MCA sign yielded interesting results. Manelfe et al found that the sign related to the severity of initial clinical neurological deficits and to ischemic changes on CT demonstrating the specificity of the sign for MCA occlusion. Nevertheless, CT evidence of MCA thrombosis did not, by itself, indicate a poor prognosis and did not rule out a favorable response to IV rtPA. Some clinicians have questioned the efficacy of IV thrombolytic therapy in patients with proximal cerebral artery occlusions compared with the results in those who have only distal branch occlusions (Caplan LP, Grotta J. N Engl J Med 1997;337:1309-1312; Caronna, JJ. Neurol Alert 1998;16:35). In fact, ECASS I patients with a CT sign of MCA thrombosis who received IV rtPA did not have an increased mortality and had a better neurological recovery than those who received placebo.
A hyperdense MCA sign on CT scan remains an important sign that may aid the clinician in reaching an etiological diagnosis in a stroke patient. Nevertheless, it does not have independent prognostic significance and its presence should not affect a decision to use thrombolytic therapy.
a. The hyperdense MCA sign has a high specificity, but low sensitivity for MCA occlusion.
b. The bilateral hyperdense MCA sign may be due to calcified atherosclerosis.
c. The hyperdense MCA sign does not predict response to IV rtPA.
d. The hyperdense MCA sign always indicates a poor outcome.
e. The hyperdense MCA sign may not be seen on later CT scans taken after day 1.