Target condition being diagnosed
About one third of all ischaemic strokes occurring in the posterior circulation of the brain (the territory supplied by the vertebral arteries) can be attributed to thromboembolism from atherosclerotic stenosis in one of the vertebral arteries. In people with posterior circulation events, the presence of a stenosis ≥ 50% in the vertebrobasilar system is associated with a higher risk of early recurrent stroke (Gulli 2009; Marquardt 2009). Although the stenosis is measured on a continuous scale, the threshold value of 50% was chosen. Accurate grading of vertebral artery stenosis is essential because of the new endovascular treatment options that are emerging.
Studies of sufficient quality measuring the accuracy of diagnosing and grading vertebral artery stenosis with noninvasive imaging techniques against the gold standard of intra-arterial digital subtraction angiography (DSA) are scarce. In a systematic review from 2007, computed tomographic angiography (CTA) and contrast enhanced magnetic resonance angiography (MRA) were most sensitive in diagnosing vertebral artery stenosis compared with duplex ultrasound (DUS) (Khan 2007). The sensitivity and specificity of CTA were 100% (95% confidence interval (CI) 15.8 to 100) and 95.2% (95% CI 83.8 to 99.4), respectively. The pooled sensitivity and specificity of contrast enhanced magnetic resonance imaging (MRI) were 93.9% (95% CI 79.8 to 99.3) and 94.8% (95% CI 91.1 to 97.3). In Khan 2007 the number of high quality studies was limited. Since 2007, several new studies of imaging of vertebral artery stenosis have been performed.
Visualisation of the vertebral artery, and especially the vertebral artery origin, is complicated by the deep, tortuous course, breathing movements and pulsations from nearby vessels. Current treatment options for vertebral artery stenosis are medical treatment, surgical revascularisation and percutaneous transluminal angioplasty with or without stenting. A Cochrane review of percutaneous transluminal angioplasty and stenting for vertebral artery stenosis concluded that the role of the different procedures in preventing stroke from vertebral artery stenosis has not been fully established (Coward 2005). This diagnostic test accuracy review is relevant, since little is known about the accuracy of the non-invasive imaging modalities for imaging of the vertebral arteries.
The main objective of this review will be to meta-analyse the diagnostic accuracy of non-invasive imaging compared with the reference standard, and to investigate potential sources of variation. A clinical correlation is not needed for this analysis, since stenosis in a vertebral artery of a patient who has had symptoms originating from pathology from the posterior circulation has the same characteristics as a stenosis in a vertebral artery of a patient who did not have symptoms.
DUS is used for assessment of the extracranial vertebral artery and can be performed with or without colour coding. Peak systolic velocity (PSV) is the most commonly used parameter for the assessment of vertebral artery stenosis, although the exact relation between PSV and the grade of stenosis has not been fully elucidated. DUS is quick and inexpensive, but very operator-dependent. Therefore, intensive training and quality control of the technicians and doctors performing the test are important factors to consider when interpreting test results.
Transcranial Doppler (TCD) and transcranial colour-coded duplex sonography (TCCD) are ultrasound neuroimaging modalities that can provide useful diagnostic information on the intracranial vertebral artery with a high degree of safety. Similar to DUS this technique is non-invasive and the diagnostic value is known to be operator-dependent. In addition, the use of TCD and TCCD is limited to the evaluation of the intracranial segments of the vertebral artery. If a severe extracranial stenosis is present, the pattern of intracranial vertebral flow may confirm this stenosis. However, the operator would not be able to localise the extracranial stenosis on TCD or TCCD alone.
CTA allows visualisation of the total vertebral artery. CTA is relatively cheap and widely available, but is contraindicated in patients with renal failure. In this review we consider imaging techniques in which contrast fluid is administered to the patient through an intravenous catheter as 'minimally invasive'.
MRA allows visualisation of the total vertebral artery similar to CTA and can be performed with or without contrast enhancement. MRI scans often prove difficult for patients suffering from claustrophobia. If a patient is unable to lie still the imaging will most likely suffer from movement artefacts that will compromise the quality and reliability of the test. MRA is contraindicated in patients with pacemakers and metallic implants. Furthermore, it is expensive.
In patients with vertebrobasilar ischaemia, intra-arterial DSA is the gold standard for diagnosing vertebral artery stenosis. The current diagnostic pathway preceding DSA varies, depending on the preferences of the local neurologist. Either DUS, TCD, (contrast enhanced) MRA, CTA or a combination of these imaging modalities is used. DSA has a small but non-negligible risk of morbidity and mortality (Hankey 1990). Consequently, if DSA is replaced by a noninvasive or minimally invasive imaging modality, the potential overall benefit of a possible treatment would increase. In the best diagnostic pathway DSA would be replaced by a single non-invasive imaging modality or the combination of one or more imaging modalities. Alternatively, one or more of the non-invasive or minimally invasive imaging modalities might be suitable for screening for vertebral artery stenosis. Another advantage of replacing DSA by (a combination of) index tests is that DSA is mostly unavailable in non-tertiary centres, whereas DUS, CT and MRI are widely available in most hospitals.
Currently, there is no standard treatment for patients with a symptomatic vertebral artery stenosis. However, there are different treatment options as reported above. If the result of the index test is false negative, the patient will not be eligible for surgical or interventional treatment. This in turn could lead to a new transient ischaemic attack (TIA) or stroke. If the result of the index test is false positive, surgical or endovascular treatment might be considered. This is expensive and invasive. However, missing a potentially treatable stenosis (i.e. false negative result) would be worse.
Intra-arterial DSA is the gold standard test to estimate stenosis in the vertebral artery. However, in line with diagnosing carotid artery stenosis, the question is whether it remains ethical to use DSA for diagnostic purposes only, due to the small but non-negligible risk of morbidity and even mortality (Hankey 1990). Therefore, non-invasive and minimally invasive tests such as DUS, TCD/TCCD, CTA, or MRA are increasingly used in the diagnosis of vertebral artery stenosis. However, unlike in the diagnosis of carotid artery stenosis (Debrey 2008; Koelemay 2004; Nederkoorn 2003; Wardlaw 2006) the pooled diagnostic accuracy is unknown. Anatomical differences between the carotid and vertebral artery (e.g. smaller size and deeper course of the vertebral artery, greater variation between the two sides of the neck) prevent extrapolation of results from diagnosing carotid artery stenosis to vertebral artery stenosis. In 2007 a systematic review was published on the same subject; since then several new studies have been published and treatment of vertebral artery stenosis has gained ground (Khan 2007).