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How Accurate is Non-Invasive Testing to Diagnose Intracranial Arterial Stenosis?
Abstract & Commentary
By Matthew E. Fink, MD, Vice Chairman, Professor of Clinical Neurology, Weill Medical College, Chief of Division of Stroke and Critical Care Neurology, NewYork-Presbyterian Hospital. Mr. Fink reports no consultant, stockholder, speaker's bureau, research, or other relationships related to this field of study.
Synopsis: TCD and MRA have a low positive predictive value in diagnosing clinically significant intracranial stenosis, but are useful as screening tests to rule-out significant lesions.
Source: Feldmann E and the SONIA Investigators. The Stroke Outcome and Neuroimaging of Intracranial Atherosclerosis (SONIA) Trial. Neurology. 2007; 68: 2099-2106.
Intracranial stenosis (ICS) causes about 70,000 ischemic strokes each year in the United States, and is more common in Hispanics, African-Americans, Japanese and Chinese compared to the U.S white population. The WASID study (Chimowitz, et al, Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005;352:1305-1316.) documented a one-year recurrent stroke risk of 22% in patients with high-grade intracranial stenosis, based on catheter angiography. Proven therapy for intracranial stenosis is currently limited to antiplatelet drugs, but the development of successful intracranial angioplasty and stenting mandates that we investigate the intracranial circulation as part of every stroke evaluation. The SONIA investigators, starting with the WASID patients, attempted to assess the accuracy of transcranial Doppler ultrasound (TCD) and magnetic resonance angiography (MRA) in diagnosing significant stenosis of the major intracranial arteries (proximal middle cerebral, carotid siphon, intracranial vertebral arteries and basilar), compared to the diagnostic gold standard, catheter angiography.
The SONIA Trial was a parallel study to the WASID trial that enrolled patients who were symptomatic from TIA or ischemic stroke and had positive TCD and/or intracranial non-contrast MRA studies before they underwent cerebral angiography. The investigators also included other patients, outside of WASID, with symptomatic ICS, if they met the same criteria. Significant stenosis of the major intracranial arteries was defined as >50% stenosis by direct caliper measurement of the MRA and angiography films by a blinded neuroradiologist at a central reading site. Stenosis on TCD was defined by measuring the time-averaged mean of the maximum velocity. A positive test was a mean velocity >100 cm/sec in the middle cerebral artery (MCA), >90 cm/sec in the internal carotid artery (ICA), or >80 cm/sec in the basilar artery (BA) or vertebral arteries (VAs).
The primary aim of SONIA was to define velocity values on TCD and anatomic abnormalities on MRA that could identify 50-99% intracranial stenosis of the MCA, ICA, BA or VA, compared to catheter angiography, with a positive predictive value (PPV) of 80%. The secondary aim was to demonstrate that TCD and/or MRA could exclude significant intracranial stenosis with a negative predictive value (NPV) of 90%. A true determination of sensitivity and specificity could not be achieved because only patients with positive TCD/MRA underwent cerebral angiography. For each patient, both normal and diseased vessels were studied and included in the analysis.
Over a 4-year period, 407 patients were enrolled, and there was corresponding TCD data for 451 vessels, and MRA data for 1310 vessels. The ethnic distribution of patients was 54% white, 33% African-American, 6% Hispanic, and 4% Asian. Mean age was 65 years, and 40% of patients were female. Angiography revealed normal studies in 1105 vessels (69%), < 50% stenosis in 141 vessels (9%), 50%-99% stenosis in 315 vessels (20%) and occlusion in 35 vessels (2%). TCD analysis revealed a PPV of 36% (CI = 27-46) and a NPV of 86% (CI = 81-89). MRA analysis showed a PPV of 59% (CI = 54-65) and a NPV of 91% (CI=89-93). If the "cut-point" for TCD velocity was increased (from 100 cm/sec to 240 cm/sec for the MCA) and the "cut-point" for MRA stenosis was increased (from 50% to 80%), the PPV was shown to increase as well, but at a cost of a decrease in the NPV. The investigators made no attempt to compare TCD to MRA, because there were too few patients who had both studies performed.
The evaluation of patients with TIA or ischemic stroke and suspected intracranial arterial stenosis is difficult, and any help that we can obtain from non-invasive testing is valuable. Few patients will undergo catheter angiography, since it is hard to justify the discomfort, cost, and risk of such studies, without a definitive treatment of proven value other than general therapies such as antiplatelet medications, statins, antihypertensives, and life style modifications. Intracranial stenting, while holding great promise for the future, is an investigational procedure that has been reserved for those patients who have recurrent symptoms after maximal medical therapy. And, intracranial stenting should only be performed in the context of a well designed clinical trial, or else we will never learn if it is a truly effective and beneficial therapy.
MRA is the most widely used non-invasive technique for assessing intracranial vascular anatomy. TCD has fallen out of favor because of variable technical results that are very much operator dependent, as well as difficulty in using an indirect physiological measurement (blood flow velocity) to assess vascular anatomy. The SONIA trial also noted that TCD was requested much less than MRA and this trend has continued. However, as the SONIA trial has so carefully reported, the PPV of MRA is only 59% in diagnosing >50% stenosis of an intracranial artery. This low predictive value is largely due to false positive studies, which is something we all grapple with on a daily basis. However, a normal MRA study carries a NPV of 91%, which may give us and our patients some comfort. The bottom line of the SONIA trial is that TCD and MRA should always be viewed as screening tests that require a confirmatory test when an abnormality is found, as long as there is an available treatment for the underlying pathology that is suspected.