Dr. Liebeskind of the University of California, Los Angeles, received consulting fees from Cerenovus, Genentech, Medtronic, and Stryker.)
Dr. Levine of the SUNY Health Science Center at Brooklyn has no relevant financial relationships to disclose.)
Ischemic complications due to cerebral angiography are relatively uncommon, yet permanent sequelae may occur. Numerous studies have documented the incidence of stroke associated with cerebral angiography, yet the underlying pathophysiologic mechanisms remain diverse. Increasing use of angiography for acute ischemic stroke and carotid revascularization may elucidate the nature of these events as periprocedural complications are more likely in those with established cerebrovascular disease. In this article, the author provides an overview of the most recent information on the topic.
• Despite refinements and modifications in technique, standardization of training, improvements in catheter design, improvements in image acquisition and processing, and the reduction of angio-toxic and neurotoxic contrast agents, neurologic complications still occur in association with cerebral angiography (Spiotta et al 2013).
• Cerebral angiography may be complicated by a diverse range of neurologic deficits.
• Preventive measures include a combination of strict adherence to meticulous technique (eg, double flush infusions within the catheter, smooth and atraumatic manipulations of guide wire and catheter, minimization of the time a catheter is positioned within a vessel) and the performance and supervision of the procedure by an experienced neuro-angiographer (Sato et al 2013).
Historical note and terminology
Inadvertent stroke due to cerebral angiography has been an important consideration from the initial clinical application of this diagnostic technique. Cerebral angiography was first developed and used by the Portuguese neurologist Egas Moniz, who in 1927 injected a solution of strontium bromide into a surgically exposed carotid artery of a patient while placing the head between an x-ray source and a silver halide-impregnated glass plate (Moniz 1927). Although this first human cerebral angiogram successfully demonstrated the intracranial arteries, the patient died a short time later, presumably due to a massive stroke (possibly related to carotid dissection). Fortunately, with this new technique, Moniz was subsequently successful in producing cerebral angiograms without severe complications after modifying the type of contrast agent used for injection.
A relatively high incidence of serious neurologic complications, attributed to dislodgment of atherosclerotic plaque or local dissection of the injected vessel, was reported during the early era of direct puncture (carotid or vertebral) cerebral angiography (Lahl and Drews 1980; Hankey et al 1990a). Early case series often did not address complications related to cerebral angiography. This led to a widely held notion that complications related to this procedure were underreported. In the 1960s, direct puncture techniques were further refined and better training was available for performance of these techniques. Although this reduced the overall complication rates related to neuroangiography, combined neurologic complication rates reported in the prospective series remained in the range of 3.9% to 14% (Allen et al 1965; Wishart 1971). Completion angiography after carotid endarterectomy may be performed with minimal complications at present (Ricco et al 2011).
Although percutaneous catheterization already had been in existence for more than 2 decades, specific application of this technique for selective cannulation of brachiocephalic vessels only began to emerge in the 1950s after Seldinger developed an easy method of attaining percutaneous transfemoral arterial access (Seldinger 1953). Within another decade, percutaneous selective catheterization techniques for cerebral angiography became more refined and practical due to the work of a variety of investigators, including Newton and colleagues, Hinck and colleagues, Hinck and Dotter, and Mani, in which significant improvements were achieved in both technical practices and available technology (eg, catheters and guide wires) (Newton et al 1966; Hinck et al 1967; Hinck and Dotter 1969; Mani 1970).
Further improvements in technique combined with a better understanding of the normal and pathologic anatomic substrate of cerebrovascular disease occurred in the late 1960s and 1970s; developments such as the first therapeutic angiographic techniques for vascular lesions of the spinal cord (Doppman et al 1968; Newton and Adams 1968) and brain (Kricheff et al 1972), systematic external carotid branch injections (Djindjian and Merlan 1978), "superselective" catheterization technique (Voigt and Djindjian 1976; Lasjaunias and Berenstein 1978), and temporary and permanent balloon occlusion of cerebral vasculature (Serbinenko 1974; Debrun et al 1978) occurred. Angiographic test occlusion may now reliably predict tolerance of planned therapeutic carotid occlusion, and such test occlusion protocols may inculcate minimal risk of stroke during the procedure (van Rooij et al 2005). These pioneering investigators established the groundwork for the development of therapeutic applications of neuroangiography. Recommendations for training requirements and credentialing may reduce complications, especially given the expansion in specialists performing cerebral angiography (Qureshi et al 2008; Spiotta et al 2013). Recent increase in use of radial access for cerebral angiography has not been associated with increased complication rates (Ghani et al 2020; Khanna et al 2020).
Another pivotal advance in the technique of cerebral angiography has been related to improvements in both ionic and eventually nonionic iodinated contrast agents, first realized in the 1950s when a new class of ionic triiodo benzol compounds was developed with more favorable water solubility, pharmacology, and iodine concentration properties (Kagstrom et al 1958). This class of contrast agents was eventually improved on by the development of chemically related nonionic triiodo benzol compounds introduced in the 1980s (Bird et al 1984; Gross-Fengels et al 1987; Skalpe 1988). These latter compounds have the theoretical advantage of decreasing adverse effects related to hyperosmolality, which has been implicated in mechanisms of systemic contrast reactions, breakdown of blood-brain barrier, and neurotoxicity (Kagstrom et al 1958; Harrington et al 1966; Jeppsson and Olin 1970; Sage et al 1983; Bird et al 1984; Skalpe 1988).
Despite the infinite number of refinements and modifications in technique, standardization of training, improvements in catheter design, improvements in image acquisition and processing, and the reduction of angio-toxic and neurotoxic contrast agents, neurologic complications still occur in association with cerebral angiography and, thus, remain a significant concern in modern clinical neurovascular practice. Therefore, the physician should always consider a proper risk-benefit analysis before referring a patient for cerebral angiography.
The increase in endovascular procedures for acute ischemic stroke provides further opportunity to study iatrogenic stroke associated with angiography. Careful case selection based on clinical data may reduce rates of angiographic complications in acute stroke (Nazliel et al 2008). Increasing use of multimodal CT/MRI and combinations of these noninvasive modalities may further reduce the risks associated with subsequent conventional angiography (Hassan et al 2013). The proliferation of noninvasive CT or MRI techniques to discern detailed vascular findings such as lenticulostriate anatomy or vasculitic changes may also concurrently decrease the use of purely diagnostic angiography (Cho et al 2008). Use of specific devices more recently introduced in practice may also beget distinct complications (eg, dissection vs. distal emboli) (Kerber et al 2007; Bose et al 2008; Yahia et al 2008). Despite these complexities and high-risk cases, overall low complication rates of 0.30% have been reported, including no strokes across 3636 diagnostic angiograms at an academic center (Fifi et al 2009). Other estimates have placed the complication rate from 0% to up to 2.6% (Lawson et al 2011; Thiex et al 2010). An evaluation of angiography during endovascular procedures for acute ischemic stroke noted a 2% rate of iatrogenic dissections (Goeggel Simonetti et al 2019). The rapid dissemination of flat panel CT now allows for immediate post-procedure imaging that readily detects hemorrhage (Doerfler et al 2015).
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