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Case series
Asymptomatic moderate carotid artery stenosis with intraplaque hemorrhage: onset of new ischemic stroke
  1. Kiyofumi Yamada1,
  2. Masanori Kawasaki3,
  3. Shinichi Yoshimura4,
  4. Yuichi Sasaki1,
  5. Shigehiro Nakahara1,
  6. Yoshikazu Sato2
  1. 1Department of Neurosurgery, Sato Daiichi Hospital, Oita, Japan
  2. 2Department of Radiology, Sato Daiichi Hospital, Oita, Japan
  3. 3Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan
  4. 4Department of Neurosurgery, Hyogo College of Medicine, Hyogo, Japan
  1. Correspondence to Dr Kiyofumi Yamada, Department of Neurosurgery, Sato Daiichi Hospital, 77-1 Hokyoji, Usa, Oita 879-0454, Japan; yamadakiyofumi{at}gmail.com

Abstract

Background The degree of stenosis of carotid arteries is recognized as an important risk factor for ischemic stroke. However, high-grade stenosis does not always cause cerebrovascular events, whereas low- to moderate-grade stenosis may often cause strokes. It has been reported that there is an association between carotid intraplaque hemorrhage (IPH) and new brain ischemic events.

Case presentation We present three patients with asymptomatic moderate carotid artery stenosis and carotid IPH who underwent both neurological and MRI at baseline and after at least 1 year's follow-up. These patients were admitted to our hospital (after 15–35 months of follow-up) because of neurological deficits. Diffusion-weighted MRI of the brain showed ipsilateral new ischemic lesions due to carotid artery plaques. The patients were treated with carotid artery stenting and discharged uneventfully.

Conclusions Whether plaques with severe stenosis already had severe stenosis at the onset of events or plaques with moderate stenosis progressed owing to an acute change, such as growth of an IPH, remains unclear, because no carotid imaging was carried out just before the events. This is the first case report which presents neurological symptoms and MRI at both baseline and follow-up in patients with asymptomatic moderate carotid artery stenosis and carotid IPH.

  • Stroke
  • MRI
  • Stenosis
  • Stent
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Background

Carotid artery stenosis is one of the major causes of ischemic stroke. Several large randomized controlled trials have established that carotid endarterectomy (CEA) or carotid artery stenting (CAS) significantly reduces stroke risk compared with medical treatment in patients with high-grade stenosis, but does not reduce stroke risk in those with low- to moderate-grade stenosis.1–5 Assessment of the risk of stroke and the criteria for surgical intervention in these randomized controlled trials have been based on the degree of stenosis.6 ,7 However, it has been reported that intraplaque hemorrhage (IPH) is associated with accelerated plaque growth, luminal narrowing, and development of symptomatic events.8 ,9 Whether plaques with severe stenosis after the onset of events already had severe stenosis at the onset of events or whether plaques with moderate stenosis progressed owing to acute change, such as the growth of IPH remains unclear, because no carotid imaging was available just before the events.

In this report, we describe three patients with asymptomatic carotid plaques with moderate stenosis and IPH who later presented neurological deficits after 15–35 months of follow-up.

Case presentation

Case 1

An 82-year-old man was referred to our department for evaluation of carotid artery stenosis. He showed no neurological deficit. He had a history of hypertension and hyperlipidemia. He was receiving a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin), a calcium channel blocker, and an angiotensin II receptor blocker (ARB). No acute infarction was seen on diffusion-weighted MRI (DW-MRI) and no stenotic lesions in the intracerebral arteries on three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA). A 3D-TOF-MRA maximum intensity projection (MIP) image of the neck showed 50% stenosis according to North American Symptomatic Carotid Endarterectomy Trial criteria with IPH in the left internal carotid artery.3 According to the guidelines for the management of asymptomatic carotid stenosis,6 ,10 the patient was treated with antiplatelet medication and a statin in an outpatient clinic. His compliance with this treatment was good.

After 35 months, he was admitted to our hospital with a history of right hemiparesis and an low-density lipoprotein (LDL) cholesterol level of 83 mg/dL. DW-MRI of the brain showed acute infarctions in the left cerebral hemisphere. 3D-TOF-MRA of the brain showed no stenotic lesions. A 3D-TOF-MRA MIP image and digital subtraction angiography (DSA) of the neck showed 80% stenosis. The degree of stenosis appeared to have progressed compared with that seen 35 months earlier. After admission, according to the guidelines for the management of symptomatic carotid stenosis,4–6 ,10 the patient was treated with CAS, and discharged uneventfully (Figure 1).

Figure 1

MRI images at baseline (A–C) and after 35 months of follow-up (D–F). Angiogram of precarotid artery stenting (CAS) (G, H) and post-CAS (I, J). (A) Diffusion-weighted MRI (DW-MRI) of the brain showed no acute ischemic lesion. (B) A three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) maximum-intensity projection (MIP) image of the left carotid artery showed moderate-grade stenosis (50%). It also illustrates a hyperintense signal indicating intraplaque hemorrhage (IPH) (arrow head). (C) An axial 3D-TOF source image demonstrates signal hyperintensity in the plaque indicating IPH (arrowhead). *Lumen of internal carotid artery. (D) DW-MRI of brain showed acute ischemic lesions (arrows). (E) A 3D-TOF-MRA MIP image of the left carotid artery changed from moderate-grade to high-grade stenosis (80%). It also illustrates a hyperintense signal indicating IPH. (F) An axial 3D-TOF source image demonstrates signal hyperintensity in the plaque indicating IPH (arrowhead). The lumen of the internal carotid artery (*) is apparently narrowed comared with that of baseline. (G) Frontal view and (H) lateral view of the pre-CAS angiogram showed high-grade left carotid artery stenosis. (I) Frontal view and (J) lateral view of the post-CAS angiogram. The left carotid artery was successfully dilated.

Case 2

An 82-year-old woman was referred to our department for evaluation of carotid artery stenosis. She showed no neurological deficit. She had a history of hypertension and hyperlipidemia. She was receiving a statin, calcium channel blocker, and ARB. There was no acute infarction on DW-MRI and no stenotic lesions in the intracerebral arteries on 3D-TOF-MRA. A 3D-TOF-MRA MIP image of the neck showed 50% stenosis with IPH in the right internal carotid artery. The patient was treated with antiplatelet medication in an outpatient clinic.

After 32 months, she was admitted with a history of left hemiparesis and dysarthria and an LDL cholesterol level of 88 mg/dL. DW-MRI of the brain showed acute infarctions in the right cerebral hemisphere. 3D-TOF-MRA of the brain showed no stenotic lesions. A 3D-TOF-MRA MIP image and DSA of the neck showed 56% stenosis with IPH in the right internal carotid artery. After admission, the patient was treated with CAS and discharged uneventfully (Figure 2).

Figure 2

MRI images at baseline (A–C) and after 32 months of follow-up (D–F). Angiogram of precarotid artery stenting (CAS) (G, H) and post-CAS (I, J). (A) Diffusion-weighted MRI (DW-MRI) of brain showed no acute ischemic lesion. (B) A three dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) maximum intensity projection (MIP) image of the right carotid artery showed moderate-grade stenosis (50%). It also illustrates a hyperintense signal indicating intraplaque hemorrhage (IPH) (arrow head). (C) An axial 3D-TOF source image demonstrates signal hyperintensity in the plaque indicating IPH (arrowhead). *Lumen of the internal carotid artery. (D) DW-MRI of brain showed acute ischemic lesions (arrows). (E) A 3D-TOF-MRA MIP image of the right carotid artery shows slight change of stenosis from 50% to 56%. It also illustrates a hyperintense signal indicating IPH. (F) An axial 3D-TOF source image demonstrates signal hyperintensity in the plaque indicating IPH (arrowhead). *Lumen of internal carotid artery. (G) Frontal view and (H) lateral view of the pre-CAS angiogram showed moderate-grade right carotid artery stenosis. (I) Frontal view and (J) lateral view of the post-CAS angiogram. The right carotid artery was successfully dilated.

Case 3

A 78-year-old man was referred to our department for evaluation of carotid artery stenosis. He showed no neurological deficit. He had a history of hypertension and hyperlipidemia. He was receiving a statin and an ARB. There was no acute infarction on DW-MRI and no stenotic lesions in the intracerebral arteries on 3D-TOF-MRA. A 3D-TOF-MRA MIP image of the neck showed 50% stenosis with IPH in the right internal carotid artery. The patient was treated with antiplatelet medication in an outpatient clinic.

After 15 months, he was admitted to our hospital with a history of left hemiparesis and an LDL cholesterol level of 102 mg/dL. DW-MRI of the brain showed acute infarctions in the right cerebral hemisphere. A 3D-TOF-MRA MIP image of the brain showed no stenotic lesions. A 3D-TOF-MRA MIP image and DSA of the neck showed 54% stenosis. After admission, the patient was treated with CAS and discharged uneventfully (Figure 3).

Figure 3

MRI images at baseline (A–C) and after 15 months of follow-up (D–F). Angiogram of precarotid artery stenting (CAS) (G, H) and post-CAS (I, J). (A) Diffusion-weighted MRI (DW-MRI) of brain showed no acute ischemic lesions. (B) A three dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA) maximum intensity projection (MIP) image of the right carotid artery shows moderate-grade stenosis (50%). It also illustrates a hyperintense signal indicating intraplaque hemorrhage (IPH) (arrow head). (C) An axial 3D-TOF source image demonstrates signal hyperintensity in the plaque indicating IPH (arrowhead). *Lumen of the internal carotid artery. (D) DW-MRI of the brain showed acute ischemic lesions (arrows). (E) A 3D-TOF-MRA MIP image of the right carotid artery shows slight change of stenosis from 50% to 54%. It also illustrates a hyperintense signal indicating IPH. (F) An axial 3D-TOF source image demonstrates signal hyperintensity in the plaque indicating IPH (arrowhead). *Lumen of the internal carotid artery. (G) Frontal view and (H) lateral view of the pre-CAS angiogram showed moderate-grade right carotid artery stenosis. (I) Frontal view and (J) lateral view of the post-CAS angiogram. The right carotid artery was successfully dilated.

Discussion

Strokes remain a leading cause of morbidity and mortality. Carotid artery stenosis is one of the major causes of ischemic stroke. However, treatment decisions are still based on the degree of stenosis. Current criteria for surgical intervention in asymptomatic patients requires 70–80% stenosis, and the benefit of CEA or CAS is controversial even in patients with asymptomatic carotid artery stenosis.11 According to the Asymptomatic Carotid Atherosclerosis Study, the stroke rate in patients with ≥60% asymptomatic carotid stenosis is about 2%/year.1 However, in cases of asymptomatic moderate carotid artery stenosis, a low stroke rate (0.6%/year) was reported during a mean follow-up of 48 months in 198 patients.12 The average annual rate of ipsilateral strokes in patients with asymptomatic carotid stenosis receiving medical treatment, such as antiplatelet drugs and statins, has fallen well below the rates in patients who undergo CEA.13

On the other hand, a growing body of literature suggests that tissue characterization of carotid plaques may provide a better means of predicting future ipsilateral cerebrovascular events than the degree of carotid artery stenosis.8 ,9 Carotid IPH plays a critical role in the progression of carotid atherosclerotic disease. The presence of IPH in carotid atherosclerotic plaques has been associated with accelerated plaque growth and luminal narrowing.8 ,9 We and other investigators reported that MRI of carotid plaque has a good sensitivity with a moderate-to-good specificity for the detection and quantification of IPH, using histology as a ‘gold standard’.14–17 According to these methods, IPH can be seen as a hyperintense signal on 3D-TOF source images and 3D-TOF-MRA MIP images of carotid plaques.

Among our cases, the degree of stenosis apparently progressed in one case and did not progress in the other two during a follow-up of 15–35 months. However, ipsilateral stroke occurred in all three cases. This suggests that the presence of carotid IPH does not always cause luminal narrowing that precedes the onset of ipsilateral stroke, and ipsilateral stroke can occur without plaque growth and luminal narrowing when carotid plaques have IPH. Therefore, it is clear that there are two types of carotid plaques that have IPH associated with ipsilateral ischemic stroke. One is the plaque with moderate stenosis after the onset of ischemic stroke, and the other is the plaque with severe stenosis after the onset of ischemic stroke. For coronary artery disease, it has been reported that the progression of coronary artery lesions can be classified into two types: type 1 vessels are characterized by sudden appearance of marked progression due to large thrombi and bleeding in plaques after plaque rupture or endothelial damage; type 2 vessels are characterized by continuous slight progression of stenosis due to plaque growth or small thrombi and bleeding in plaques after plaque rupture. Acute myocardial infarction occurs only in type 1 vessels. This process is different from carotid artery stenosis and is a unique process. It provides new insight into the mechanism of carotid artery disease.18 ,19

Two previous studies using MRI have reported an association between new cerebrovascular events and carotid IPH at baseline in patients with asymptomatic moderate carotid artery stenosis. Takaya et al20 reported that 14 cerebrovascular events (3.0%/year) occurred (four transient ischemic attacks, six strokes, and four amaurosis fugax) during a mean follow-up of 38 months in 154 patients with asymptomatic moderate carotid artery stenosis with IPH at baseline. Singh et al21 reported that six ipsilateral carotid events (8.3%/year) occurred (four transient ischemic attacks and two strokes) in 36 patients with asymptomatic moderate carotid artery stenosis and IPH, whereas there were no clinical events in the carotid arteries without IPH during a mean follow-up of 24 months. Both studies have shown that IPH at baseline is associated with future ipsilateral cerebrovascular events with HRs of 3.621 and 5.2,20 suggesting that IPH is a promising predictor of future cerebrovascular events in patients with moderate carotid stenosis. However, both studies only discussed the association between the presence of carotid IPH at baseline and new ischemic stroke, and did not discuss the stenotic change or stenotic process. In our report, we showed plaques with asymptomatic moderate stenosis and IPH both at baseline and at the onset of neurological deficits.

Whether plaques with severe stenosis after the onset of ischemic stroke already had severe stenosis at the onset of stroke or whether plaques with moderate stenosis progressed owing to acute change, such as growth of IPH at the onset of an event, remains unclear, because no carotid imaging was carried out just before the events. However, this is the first case report presenting neurological symptoms and MRI at both baseline and follow-up in patients with asymptomatic moderate carotid artery stenosis and carotid IPH.

The study has limitations, because the patients were studied retrospectively and the number of cases is small, therefore, larger prospective studies are warranted to determine the value of carotid IPH in predicting strokes in patients with asymptomatic moderate carotid artery stenosis.

Conclusion

We have described three patients who had asymptomatic moderate carotid stenosis with carotid IPH and who subsequently experienced ipsilateral stroke after 15–35 months despite treatment with antiplatelet drugs and statins. Unlike coronary artery disease, two types of carotid plaque were seen where IPH was associated with ipsilateral ischemic stroke. One was plaque with moderate stenosis after the onset of ischemic stroke, and another was plaque with severe stenosis after the onset of ischemic stroke. Although the complex mechanisms of onset of ipsilateral strokes are still unknown, these cases provide new insight into the carotid plaques that cause ipsilateral strokes.

References

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Footnotes

  • KY and MK contributed equally.

  • Contributors KY was responsible for the MR image review and interpretation of data, and preparation of the manuscript. MK assisted in data interpretation and revised the critical content of the manuscript. SY assisted in development of the study design and interpretation of data. YuS, SN, and YoS revised the manuscript. All authors read the manuscript and approved its submission.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by the local institutional review board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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