Carotid Stenosis and Stroke: Medicines, Stents, Surgery—“Wait-and-See” or Protect?

Carotid Stenosis and Stroke Mechanisms

Stroke, a vascular disease of the brain, is the most common cause of complex disability and a major cause of death worldwide.[1] [2] [3] Stroke, with its major negative impact on affected individuals, their families, and the society, is one of the most dreaded events in life.[4] Nearly half of stroke survivors will be disabled and dependent, with one in seven requiring permanent institutional care.[4] Because of the profound negative effect of stroke-related mental and physical disabilities upon quality of life, a significant proportion of stroke victims indicate that they would have preferred death over their life after stroke.[4] Only a minority of strokes are preceded by a transient ischemic attack (TIA), a warning that enables timely intervention to reduce the risk of permanent brain damage.[5] [6] Over 80% of strokes occur without any clinical warning.[6] Hence there is a fundamental role for effective preventive measures.[6] [7] [8] Optimal stroke management should be preventive rather than reactive to the devastating event that has already occurred.[5] [7] [8] Despite unquestionable progress in pharmacologic and nonpharmacologic prevention, the burden of cardiovascular disease (including stroke) will not be decreasing—but rather increasing—over the next 25 years.[1] Recent stroke burden estimates for Europe indicate an increase in stroke incidence of +3% by 2047, and an increase by ≈30%% of the number of people living with stroke.[9]

Atherosclerotic carotid artery stenosis is a modifiable, major mechanistic risk factor of ischemic stroke.[2] [10] Plaque rupture and/or erosion can lead to focal thrombus formation that may occlude the lumen, causing a stroke related to hemodynamic compromise.[10] [11] [12] [13] [14] Thrombotic occlusion of the internal carotid artery is poorly responsible to intravenous thrombolysis and is associated with large infarct size and poor functional outcome.[14] [15] [16] [17] Another stroke mechanism is atherothromboembolism to the brain, resulting in occlusion of an intracranial branch vessel(s) and infarction of the brain tissue supplied by these branches.[12] [18] Real-life contemporary scenarios of acute ischemic stroke due to atherothrombotic carotid stenosis are demonstrated in [Fig. 1] (all patients presenting with acute stroke of carotid origin within one month).

Fig. 1 Scenarios of acute ischemic stroke due to atherothrombotic carotid stenosis (patients presenting within one month). This figure presents three types of ischemic stroke, mechanistically related to atherothrombotic carotid stenosis: Panel I exemplifies acute ischemic stroke due to (sub-)occlusion of the carotid artery (extracranial segment) with a large thrombus originating from the atherosclerotic lesion. Panel II shows a tight stenosis as an underlying mechanism. Panel III demonstrates a “tandem” lesion stroke with migration of part of the internal carotid origin thrombus (stenosis progression to thrombotic occlusion) into the intracranial vasculature. Examples are taken from consecutive patients with acute ischemic stroke due to carotid stenosis. The strokes in patients I–III presented without any prior warning symptom(s), consistent with ≈80% of stroke presentations.[6] The imaging timeline is from top to bottom. Cerebral images are in the axial view, except III-D2 that is a coronal presentation. All carotid images are in the coronal view. In patients I and II, the left hemisphere is dominant; in patient III, the right hemisphere. Stenosis severity was 74% (by lumen area)/56% (diameter stenosis) in patient I, 87% (by lumen area)/64% (diameter stenosis) in patient II, and 78% (by lumen area)/61% (diameter stenosis) in patient III.[29] [30] Yellow stars (I-A, III-B1) in patients I and III indicate early cerebral ischemia on cerebral computed tomography (CT) at the time of presentation. In patient II, diffusion-weighted magnetic resonance imaging on admission (II-A1/A2) showed diffusion restriction (hyperintense areas) in the left hemisphere. The lesions were also visible on fluid-attenuated inversion recovery imaging, consistent with established cerebral damage. Patients I and III received intravenous thrombolytic therapy (IVT) which, in both cases, was clinically ineffective, consistent with reported recanalization rates of <10% in carotid occlusion strokes. Patient II presented beyond the 4.5 hour time window for thrombolysis. Yellow arrows depict the culprit (carotid) lesion (I-B1/B2, II-B1/B2, III-B2). Red arrowheads (all B images and III-C) indicate thrombus. Images in C show the CT-angiography at the time of presentation. All three patients show presence of intracranial collaterals; those, however, are rarely able to sustainably compensate an abrupt carotid artery occlusion. Red arrows (D) show the infarcted area at discharge. White arrows (III-D1/D2) depict hemorrhagic transformation that occurred in patient III. Clinical outcomes are provided at the bottom of the figure. A modified Rankin score (mRS) of 2 indicates slight disability (patient able to look after their own affairs without assistance, but unable to carry out all previous activities); mRS 3 signifies moderate disability (patient requires some help, but is able to walk unassisted); mRS 4 represents moderately severe disability (patient unable to attend to own bodily needs without assistance, and unable to walk unassisted). The National Institutes of Health Stroke Scale (NIHSS) represents a clinical stroke severity scale (≤6 minor stroke; >6 major stroke). Extracranial thrombotically active carotid plaque is a major, mechanistic risk factor for ischemic stroke.[10] Strokes in patient I and patient III were likely preventable with low-risk revascularization[20] [57] [58] on top of MMT. Note that the presence of PAD or CAD increases the risk of CS while diabetes (patient I) is an important risk factor for stroke in CS.[35] [36] [37] Patient III was not revascularized due to a wide-spread belief (despite lack of data) in a sufficient MMT protection against CS-related stroke (see text for references). After the stroke, patients I and III were no longer suitable for carotid revascularization due to major loss of cerebral tissue with a mRS ≥3, resulting in a high risk-to-benefit ratio for intervention. Patient II subsequently underwent uncomplicated endovascular revascularization of the culprit lesion 12 days after the event; this did not resolve his pronounced aphasia and stroke-related neurological deficits but would reduce the risk of another stroke. Red arrowheads indicate thrombus. CAD, coronary artery disease; CS, carotid artery stenosis; LECA, left external carotid artery; LICA, left internal carotid artery; MMT, maximal medical therapy;[20] [53] NSTEMI, non-ST-elevation myocardial infarction; Occl, occlusion; PAD, peripheral arterial disease; RECA, right external carotid artery; RICA, right internal carotid artery; RMCA, right middle cerebral artery.

Publication History

Received: 11 November 2021

Accepted: 27 September 2022

Accepted Manuscript online:
28 September 2022

Article published online:
10 July 2024

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