- Email: [email protected]
Manual Aspiration Thrombectomy in Patients with Acute Stroke-Related Calcified Cerebral Emboli
ARTICLE IN PRESS
Manual Aspiration Thrombectomy in Patients with Acute Stroke-Related Calcified Cerebral Emboli Esther Koh,
MD,
Hyo Sung Kwak,
MD, PhD,
and Gyung-Ho Chung,
MD, PhD
Objective: The aim of this study was to evaluate the effectiveness of mechanical aspiration thrombectomy (MAT) in patients with acute ischemic stroke from calcified cerebral emboli. Methods: Procedural results were reviewed for acute stroke patients with clinically neurological deficits who underwent recanalization from October 2012 through September 2015. Initial imaging studies and cerebral angiography were analyzed. Results: Of the total number of patients with acute stroke, 5 patients were confirmed to have acute ischemic stroke by calcified cerebral emboli. On initial brain computed tomographic imaging, all patients showed small, dense single calcifications in the middle cerebral artery with no definitive ischemic lowdensity lesions (M1: 3, M2: 2, mean size: 4.8 mm). All patients had angiographic findings of filling defects from calcified emboli. Four patients had good collateral flow and two had continuous distal flow. All patients underwent MAT using a Penumbra catheter (Penumbra Inc., Alameda, CA). MAT did not remove calcified emboli in all patients. Two patients with good collateral flow had favorable functional outcomes (modified Rankin Scale score ≤2). Four patients had diffuse calcification in the aortic arch, carotid artery, and aortic valve. Conclusions: Cerebral angiography supports a diagnosis of stroke when calcified cerebral emboli have contrast-filling defects and a degree of vascular occlusion. However, in this study, MAT was not an effective treatment for patients with calcified cerebral emboli because of hardness of the calcified plaque and packing into the arterial lumen. Key Words: Stroke—calcified embolus—cerebral angiography—mechanical thrombectomy. © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Introduction Calcified cerebral embolus is reported to be a cause of acute cerebral infarction. Although this condition is rare, From the Department of Radiology, Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju-si, Jeollabukdo, Republic of Korea. Received March 9, 2016; revision received June 10, 2016; accepted July 2, 2016. This paper was supported by Fund of Biomedical Research Institute, Chonbuk National University Hospital. Address correspondence to Hyo Sung Kwak, MD, PhD, Department of Radiology, Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, 567 Baekje-daero, deokjin-gu, Jeonju-si, Jeollabuk-do, 561-756, Republic of Korea. E-mail: [email protected]. 1052-3057/$ - see front matter © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.07.005
identifying the embolic source is clinically important for proper treatment. Spontaneous calcified cerebral emboli occur more frequently than iatrogenic emboli, which may be caused by procedures such as cardiac catheterization that causes valve injury, cardiac massage, or chiropractic neck manipulation.1-3 Proper identification can guide treatment to prevent future embolic events, neurological impairment, and death. Calcified cerebral emboli can be easily detected by noncontrast brain computed tomography (CT).2,4 Although noncontrast CT is a good imaging modality for identifying calcification, calcified emboli are often misdiagnosed or ignored. Cerebral angiography is a confirmative diagnostic method for stroke. Cerebral emboli show as contrast-filling defects with or without delayed distal flow. Cerebral angiography is also performed for thrombolytic treatment or mechanical thrombectomy. Several studies report controversial results for thrombolytic therapy for the immediate treatment of calcified embolic infarctions. The effectiveness of thrombolytic
Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2016: pp ■■–■■
1
ARTICLE IN PRESS E. KOH ET AL.
2
therapy may be limited by the density of the calcified embolic lesions and the risk of hemorrhage.5-7 Mechanical embolectomy is a treatment for vascular recanalization that can save time by instantly removing embolic material.8 However, mechanical recanalization also has risks of cerebral complications such as vascular rupture and cerebral hemorrhage.4 The purpose of the present study was to assess the location, size, shape, and source of calcified cerebral emboli and to evaluate the effectiveness of mechanical aspiration thrombectomy (MAT) in 5 patients.
Methods The institutional review board approved the study. Consent for pharmacological or mechanical thrombolytic treatment was obtained from patients’ legal representatives. Between October 2012 and September 2015, we retrospectively reviewed noncontrast brain CT imaging of acute stroke patients in our hospital. Acute stroke patients were diagnosed with clinically neurological deficits using brain imaging such as CT, magnetic resonance imaging (MRI), and cerebral angiography. Five patients with acute cerebral infarction caused by calcified emboli were identified by initial brain CT. These patients had no clinical history of previous brain trauma or cerebral infarction. All patients were examined by initial CT at our hospital for evaluation of cerebral hemorrhage. On admission to the emergency center, the patients were assessed by a stroke neurologist using the National Institutes of Health Stroke Scale (NIHSS) score. The patients underwent cerebral angiography for MAT. We performed MAT using a Penumbra reperfusion catheter (Penumbra Inc., Alameda, CA). Routine cerebral angiography was performed before treatment to evaluate collateral flow. An 8F introducer sheath (Super Arrow-Flex; Arrow International, Reading, PA) and an inner 100-cm-long 8F guide catheter (Guider Softip; Boston Scientific, Natick, MA) were placed in the common carotid artery to enable the approach of the Penumbra catheter. The Penumbra catheter was advanced until it reached the embolus. A 1.7F microcatheter was introduced coaxially beyond the occlusion and
local angiography was performed to predict the original path of the occluded vessel and inspect the occlusion outline. We gently advanced the Penumbra catheter into the thrombus until it wedged tightly. Subsequently, the microcatheter and microguidewire were removed and a 20-mL syringe was connected to the proximal hub of the Penumbra catheter. Continuous manual aspiration was performed by maintaining a vacuum state between the tip of Penumbra catheter and the thrombus while gently withdrawing the Penumbra catheter through the guide catheter. Potential calcified embolic sources were assessed by reviewing patients’ medical records and all imaging. We also reviewed the success of mechanical recanalization. All patients underwent follow-up CT or MRI more than once. We reviewed medical records to collect demographic, clinical, and angiographic data. Degree of collateral flow was defined as good or poor according to visualization of the distal branch. NIHSS scores were measured on admission and at discharge, and modified Rankin scale (mRS) scores were checked on admission and at 3 months for all patients. A favorable outcome was defined as an mRS score of 2 or lower. The location, long-axis size, and shape of calcified emboli were analyzed.
Results From October 2012 to September 2015, we performed cerebral angiography and endovascular treatment in approximately 450 acute stroke patients, including 193 with isolated middle cerebral artery (MCA) occlusion. Of the total number of patients with acute stroke, only 5 patients (1.1%) were diagnosed with calcified embolic stroke. During these periods, the successful recanalization rate by single Penumbra in patients with isolated MCA occlusion was 82.9%, and favorable clinical outcome (mRS score ≤2) was 60.0%. Demographic, clinical, and angiographic findings in 5 patients are shown in Tables 1 and 2. Neurological examination of all patients revealed hemiparesis and mildto-moderate dysarthria. The median NIHSS score at admission was 9 (range 8-16). On initial brain CT imaging,
Table 1. Summary of patient demographics and clinical findings before and after recanalization therapy
No. 1 2 3 4 5
Age (years)
Sex
Location
74 35 86 37 77
F M M F M
M2 M1 M1 M1 M2
Side
Onset-todoor time (min)
Onset-toneedle time (min)
Procedure time (min)
IVrtPA
Initial NIHSS score
Initial mRS score
NIHSS score at discharge
mRS score at 3 months
Right Left Right Left Left
30 60 120 240 30
120 120 190 290 60
30 25 35 30 25
Y Y Y N Y
9 12 8 15 4
4 3 4 4 4
2 2 6 15 4
1 1 3 4 4
Abbreviations: F, female; IV, intravenous; M, male; mRS, modified Rankin Scale; N, no; NIHSS, National Institutes of Health Stroke Scale; rtPA, recombinant tissue plasminogen activator; Y, yes.
ARTICLE IN PRESS ACUTE STROKE-RELATED CALCIFIED CEREBRAL EMBOLI
3
Table 2. Summary of clinical and radiological findings
Underlying disease
Angiographic findings
Calcified nodules
Continuous Filling Collateral flow of Size No. HTN DM CRF Hyperparathyroidism defect flow distal artery (mm) 1 2 3 4 5
+ − − − +
+ − − − +
− − − + −
− − − + −
+ + + + +
Good Good Poor Good Good
− − − + +
4.3 3.4 7.0 6.0 3.5
Shape Oval Oval Tubular Oval Round
Risk factor: source of calcified emboli
Carotid Aortic Cardiac artery arch valve + − + − +
+ − + + +
+ − + + +
Abbreviations: CRF, chronic renal failure; DM, diabetes mellitus; HTN, hypertension.
all patients showed small, dense single calcifications in the MCA with no definitive ischemic low-density lesions (M1: 3 and M2: 2). The mean size of calcified emboli was 4.3 mm (range 3.4-7.0 mm). Of the 5 patients, two were misdiagnosed as having parenchymal calcification by an experienced neuroradiologist. CT angiographies to evaluate stroke patients showed MCA obstructions by calcified emboli. The time from symptom onset to admission was 30240 minutes (median, 60 minutes) and the time from admission to femoral puncture was 30-90 minutes (median, 60 minutes). The median procedure time was 30 minutes (range, 25-35 minutes). Four patients received intravenous tissue plasminogen activator therapy before angiography. The initial mRS score at admission was 3-4 (median, 4). All patients had angiographic findings of filling defects from calcified emboli. Four patients had good collateral flow and two had continuous distal flow. All patients underwent MAT using a Penumbra reperfusion catheter as first-line therapy. However, MAT did not remove calcified emboli in all patients. CT images performed after cerebral angiography showed low-density infarctions in the MCA territory and no distal migration of calcified emboli. At discharge, the median NIHSS score was 4 (range, 2-15). Two patients with good collateral flow had favorable functional outcomes (mRS score ≤2). No hospital or 3-month mortality occurred. Potential embolic sources were identified using echocardiography, sonography, and CT angiography. Four patients had diffuse calcification in the aortic arch, carotid artery, and aortic valve. Of these patients, one had an ulcerated calcified nodule on carotid MRI and histopathological findings. One patient did not appear to have any calcified lesions on imaging studies.
Representative Case A 77-year-old man (patient 5) with dysarthria and rightsided weakness was admitted to our neurology department
via the emergency medical center. The onset-to-door time was 30 minutes. The NIHSS score was 4. The patient had a history of hypertension and had been taking medication for 20 years. The patient’s initial noncontrast brain CT scan showed a small calcified lesion of approximately 3.5 mm in the left M2 inferior division (Fig 1, A). Stroke MRI showed diffusion restriction and a low–ADCsignal lesion of the left MCA territory, consistent with acute cerebral infarction (Fig 1, B). Initial cerebral angiography showed a filling defect in the inferior branch of the left MCA with delayed distal flow (Fig 1, C). The microcatheter was introduced into the occlusion site of the left MCA and the Penumbra reperfusion catheter was advanced to the embolus. MAT failed because of the hardness of the calcified embolic material. After 2 days, carotid plaque MRI showed eccentric calcified thickening with intraplaque hemorrhage in the internal carotid artery (ICA) orifice and an unstable calcified nodule with a small ulcerative lesion in the left ICA orifice (Fig 1, D). No visible cardiac valve calcification was observed on transthoracic echocardiography. Cardiac CT angiogram showed diffuse atherosclerotic changes from the ascending aorta to the internal iliac artery. Carotid plaque MRI showed a calcified hemorrhagic plaque in the left ICA orifice. We presumed the calcified embolic source was from the left ICA orifice because calcified nodules in the left ICA orifice are unstable, ulcerative lesions. The patient underwent a left carotid endarterectomy. We found an ulcerative, hemorrhagic, calcified nodule on histopathological investigation.
Discussion We performed MAT in patients with calcified cerebral emboli on CT and cerebral angiography. However, MAT using a Penumbra reperfusion catheter did not result in the removal of calcified cerebral emboli in any patient. Two patients with good collateral flow had favorable functional outcomes (mRS score ≤2). Calcified cerebral embolus is an uncommon complication of calcified vascular diseases such as aortic plaques,
ARTICLE IN PRESS 4
E. KOH ET AL.
Figure 1. A 77-year-old man with a calcified cerebral embolus in an inferior branch of the left MCA. (A) Noncontrast brain CT scan showing an approximately 2-mm calcified lesion without brain parenchymal lesion (arrow). (B) Diffusion-weighted image showing diffusion restriction in the inferior division territory of the left MCA. (C) Cerebral angiography showing a filling defect in the inferior branch of the left MCA with delayed distal flow (arrow). (D) Axial image of time-of-flight MR angiography showing a calcified nodule in the left internal carotid artery orifice (arrow). Abbreviation: MCA, middle cerebral artery.
valvular calcification, or carotid plaques. Most patients have multiple calcifications in the cardiac valve, aortic arch, and carotid artery.2,4 Although migration of calcified plaque during heart catheterization, carotid artery manipulation, or cardiopulmonary resuscitation occurs in some patients, most cerebral events result from spontaneous
migration of calcified emboli.2,4 In our study, 4 patients (80%) had multiple calcified plaques and had acute ischemic strokes after spontaneous migration of calcified emboli. Spontaneous migration of cardiovascular calcification is probably due to ulceration and detachment of plaques under high blood pressure.3 In our study, 1 patient
ARTICLE IN PRESS ACUTE STROKE-RELATED CALCIFIED CEREBRAL EMBOLI
had an ulcerative, unstable calcified nodule in the ICA orifice. We identified the spontaneous migration of the calcified nodule with carotid plaque MRI and histopathological findings. Early recanalization following large-vessel occlusion is associated with improved clinical outcomes from acute ischemic stroke.9,10 MAT using a flexible aspiration catheter is an alternative method for opening blocked vessels.11-13 With the introduction of easily trackable and large aspiration catheters, recanalization rates and functional outcomes of MAT have become comparable to stentbased thrombectomy.14 Some studies report successful mechanical recanalization of calcified embolisms.15,16 In our study, MAT failed for all patients with calcified cerebral emboli because of hard emboli and packing of calcified emboli into the vessel lumen. The mean size of calcified emboli in the present study was 4.3 mm, which was larger than that in a previous study.2 We did not try stent-based thrombectomy because no microcatheter passage was available for stent deployment into the distal portion of occluded vessels. Walker et al2 reported the clinical outcomes for patients with calcified cerebral emboli. Residual neurological impairment from calcified emboli occurred in 33% of patients, complete neurological recovery was seen in 29%, and 16% died during initial hospitalization. Of 4 patients with good collateral flow in our study, two (50%) had favorable functional outcomes (mRS score ≤2). No hospital or 3-month mortality occurred. The recurrence rate for embolic infarction is 43% for patients with calcified emboli.2 Therefore, identifying embolic sources is important for determining appropriate treatment. However, in our study, most patients have multiple calcifications in the cardiovascular system. Therefore, surgical removal of all calcified plaques in the cardiovascular system is impossible. For patients with presumed embolic sources such as carotid calcified plaques, removal through carotid endarterectomy or carotid stenting is necessary. In conclusion, cerebral angiography supports a diagnosis of stroke when calcified cerebral emboli show contrast-filling defects, degrees of vascular occlusion, and collateral flow. However, in the present study, MAT in patients with calcified cerebral emboli was not an effective treatment because of hardness of calcified plaque and packing into the arterial lumen. These findings support the need for other options for recanalization of occluded vessels by calcified emboli in patients with acute ischemic stroke and workup of imaging studies to establish the presumed source of emboli.
5
References 1. Dandamudi VS, Thaler DE, Malek AM. Cerebral embolus following chiropractic manipulation in a patient with a calcified carotid artery. J Neuroimaging 2013;23:429-430. 2. Walker BS, Shah LM, Osborn AG. Calcified cerebral emboli, a “do not miss” imaging diagnosis. 22 new cases and review of the literature. AJNR Am J Neuroradiol 2014;35:1515-1519. 3. Rancurel G, Marelle L, Vincent D, et al. Spontaneous calcific cerebral embolus from a calcific aortic stenosis in a middle cerebral artery infarct. Stroke 1989;20:691-693. 4. Christian BA, Kirzeder DJ, Boyd J, et al. Showered calcific emboli to the brain, the “salted pretzel” sign, originating from the ipsilateral internal carotid artery causing acute cerebral infarction. Stroke 2009;40:e319-e321. 5. Kavanagh EC, Fenton DM, Heran MK, et al. Calcified cerebral emboli. AJNR Am J Neuroradiol 2006;27:19961999. 6. Okazaki S, Sakaguchi M, Sugiyama Y, et al. Ineffective thrombolytic therapy for calcified cerebral emboli originated from calcified internal carotid artery stenosis. Rinsho Shinkeigaku 2009;49:281-284. 7. Yoneyama T, Nakano S, Kawano H, et al. Combined direct percutaneous transluminal angioplasty and low-dose native tissue plasminogen activator therapy for acute embolic middle cerebral artery trunk occlusion. AJNR Am J Neuroradiol 2002;23:277-281. 8. Molina CA, Saver JL. Extending reperfusion therapy for acute ischemic stroke: emerging pharmacological, mechanical, and imaging strategies. Stroke 2005;36:23112320. 9. Rha JH, Saver JL. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke 2007;38:967-973. 10. Saver JL, Jahan R, Levy EI, et al. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischemic stroke (SWIFT): a randomized, parallel-group, non-inferiority trial. Lancet 2012;380:1241-1249. 11. Kang DH, Hwang YH, Kim YS, et al. Direct thrombus retrieval using the reperfusion catheter of the penumbra system: forced-suction thrombectomy in acute ischemic stroke. AJNR Am J Neuroradiol 2011;32:283-287. 12. Jankowitz B, Aghaebrahim A, Zirra A, et al. Manual aspiration thrombectomy: adjunctive endovascular recanalization technique in acute stroke interventions. Stroke 2012;43:1408-1411. 13. Kim YS, Kwak HS, Chung GH, et al. Manual aspiration thrombectomy using the Penumbra catheter in patients with acute M1 occlusion: a single-center study. Interv Neuroradiol 2015;21:694-699. 14. Turk AS, Frei D, Fiorella D, et al. ADAPT FAST study: a direct aspiration first pass technique for acute stroke thrombectomy. J Neurointerv Surg 2014;6:260-264. 15. Fassa AA1, Mazighi M, Himbert D, et al. Successful endovascular stroke rescue with retrieval of an embolized calcium fragment after transcatheter aortic valve replacement. Circ Cardiovasc Interv 2014;7:125-126. 16. Ramírez-Moreno JM, Trinidad-Ruiz M, Ceberino D, et al. Mechanical thrombectomy during ischaemic stroke due to a calcified cerebral embolism. Neurología 2015;21:S213S4853.
Manual Aspiration Thrombectomy in Patients with Acute Stroke-Related Calcified Cerebral Emboli Esther Koh,
MD,
Hyo Sung Kwak,
MD, PhD,
and Gyung-Ho Chung,
MD, PhD
Objective: The aim of this study was to evaluate the effectiveness of mechanical aspiration thrombectomy (MAT) in patients with acute ischemic stroke from calcified cerebral emboli. Methods: Procedural results were reviewed for acute stroke patients with clinically neurological deficits who underwent recanalization from October 2012 through September 2015. Initial imaging studies and cerebral angiography were analyzed. Results: Of the total number of patients with acute stroke, 5 patients were confirmed to have acute ischemic stroke by calcified cerebral emboli. On initial brain computed tomographic imaging, all patients showed small, dense single calcifications in the middle cerebral artery with no definitive ischemic lowdensity lesions (M1: 3, M2: 2, mean size: 4.8 mm). All patients had angiographic findings of filling defects from calcified emboli. Four patients had good collateral flow and two had continuous distal flow. All patients underwent MAT using a Penumbra catheter (Penumbra Inc., Alameda, CA). MAT did not remove calcified emboli in all patients. Two patients with good collateral flow had favorable functional outcomes (modified Rankin Scale score ≤2). Four patients had diffuse calcification in the aortic arch, carotid artery, and aortic valve. Conclusions: Cerebral angiography supports a diagnosis of stroke when calcified cerebral emboli have contrast-filling defects and a degree of vascular occlusion. However, in this study, MAT was not an effective treatment for patients with calcified cerebral emboli because of hardness of the calcified plaque and packing into the arterial lumen. Key Words: Stroke—calcified embolus—cerebral angiography—mechanical thrombectomy. © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.
Introduction Calcified cerebral embolus is reported to be a cause of acute cerebral infarction. Although this condition is rare, From the Department of Radiology, Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju-si, Jeollabukdo, Republic of Korea. Received March 9, 2016; revision received June 10, 2016; accepted July 2, 2016. This paper was supported by Fund of Biomedical Research Institute, Chonbuk National University Hospital. Address correspondence to Hyo Sung Kwak, MD, PhD, Department of Radiology, Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, 567 Baekje-daero, deokjin-gu, Jeonju-si, Jeollabuk-do, 561-756, Republic of Korea. E-mail: [email protected]. 1052-3057/$ - see front matter © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.07.005
identifying the embolic source is clinically important for proper treatment. Spontaneous calcified cerebral emboli occur more frequently than iatrogenic emboli, which may be caused by procedures such as cardiac catheterization that causes valve injury, cardiac massage, or chiropractic neck manipulation.1-3 Proper identification can guide treatment to prevent future embolic events, neurological impairment, and death. Calcified cerebral emboli can be easily detected by noncontrast brain computed tomography (CT).2,4 Although noncontrast CT is a good imaging modality for identifying calcification, calcified emboli are often misdiagnosed or ignored. Cerebral angiography is a confirmative diagnostic method for stroke. Cerebral emboli show as contrast-filling defects with or without delayed distal flow. Cerebral angiography is also performed for thrombolytic treatment or mechanical thrombectomy. Several studies report controversial results for thrombolytic therapy for the immediate treatment of calcified embolic infarctions. The effectiveness of thrombolytic
Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2016: pp ■■–■■
1
ARTICLE IN PRESS E. KOH ET AL.
2
therapy may be limited by the density of the calcified embolic lesions and the risk of hemorrhage.5-7 Mechanical embolectomy is a treatment for vascular recanalization that can save time by instantly removing embolic material.8 However, mechanical recanalization also has risks of cerebral complications such as vascular rupture and cerebral hemorrhage.4 The purpose of the present study was to assess the location, size, shape, and source of calcified cerebral emboli and to evaluate the effectiveness of mechanical aspiration thrombectomy (MAT) in 5 patients.
Methods The institutional review board approved the study. Consent for pharmacological or mechanical thrombolytic treatment was obtained from patients’ legal representatives. Between October 2012 and September 2015, we retrospectively reviewed noncontrast brain CT imaging of acute stroke patients in our hospital. Acute stroke patients were diagnosed with clinically neurological deficits using brain imaging such as CT, magnetic resonance imaging (MRI), and cerebral angiography. Five patients with acute cerebral infarction caused by calcified emboli were identified by initial brain CT. These patients had no clinical history of previous brain trauma or cerebral infarction. All patients were examined by initial CT at our hospital for evaluation of cerebral hemorrhage. On admission to the emergency center, the patients were assessed by a stroke neurologist using the National Institutes of Health Stroke Scale (NIHSS) score. The patients underwent cerebral angiography for MAT. We performed MAT using a Penumbra reperfusion catheter (Penumbra Inc., Alameda, CA). Routine cerebral angiography was performed before treatment to evaluate collateral flow. An 8F introducer sheath (Super Arrow-Flex; Arrow International, Reading, PA) and an inner 100-cm-long 8F guide catheter (Guider Softip; Boston Scientific, Natick, MA) were placed in the common carotid artery to enable the approach of the Penumbra catheter. The Penumbra catheter was advanced until it reached the embolus. A 1.7F microcatheter was introduced coaxially beyond the occlusion and
local angiography was performed to predict the original path of the occluded vessel and inspect the occlusion outline. We gently advanced the Penumbra catheter into the thrombus until it wedged tightly. Subsequently, the microcatheter and microguidewire were removed and a 20-mL syringe was connected to the proximal hub of the Penumbra catheter. Continuous manual aspiration was performed by maintaining a vacuum state between the tip of Penumbra catheter and the thrombus while gently withdrawing the Penumbra catheter through the guide catheter. Potential calcified embolic sources were assessed by reviewing patients’ medical records and all imaging. We also reviewed the success of mechanical recanalization. All patients underwent follow-up CT or MRI more than once. We reviewed medical records to collect demographic, clinical, and angiographic data. Degree of collateral flow was defined as good or poor according to visualization of the distal branch. NIHSS scores were measured on admission and at discharge, and modified Rankin scale (mRS) scores were checked on admission and at 3 months for all patients. A favorable outcome was defined as an mRS score of 2 or lower. The location, long-axis size, and shape of calcified emboli were analyzed.
Results From October 2012 to September 2015, we performed cerebral angiography and endovascular treatment in approximately 450 acute stroke patients, including 193 with isolated middle cerebral artery (MCA) occlusion. Of the total number of patients with acute stroke, only 5 patients (1.1%) were diagnosed with calcified embolic stroke. During these periods, the successful recanalization rate by single Penumbra in patients with isolated MCA occlusion was 82.9%, and favorable clinical outcome (mRS score ≤2) was 60.0%. Demographic, clinical, and angiographic findings in 5 patients are shown in Tables 1 and 2. Neurological examination of all patients revealed hemiparesis and mildto-moderate dysarthria. The median NIHSS score at admission was 9 (range 8-16). On initial brain CT imaging,
Table 1. Summary of patient demographics and clinical findings before and after recanalization therapy
No. 1 2 3 4 5
Age (years)
Sex
Location
74 35 86 37 77
F M M F M
M2 M1 M1 M1 M2
Side
Onset-todoor time (min)
Onset-toneedle time (min)
Procedure time (min)
IVrtPA
Initial NIHSS score
Initial mRS score
NIHSS score at discharge
mRS score at 3 months
Right Left Right Left Left
30 60 120 240 30
120 120 190 290 60
30 25 35 30 25
Y Y Y N Y
9 12 8 15 4
4 3 4 4 4
2 2 6 15 4
1 1 3 4 4
Abbreviations: F, female; IV, intravenous; M, male; mRS, modified Rankin Scale; N, no; NIHSS, National Institutes of Health Stroke Scale; rtPA, recombinant tissue plasminogen activator; Y, yes.
ARTICLE IN PRESS ACUTE STROKE-RELATED CALCIFIED CEREBRAL EMBOLI
3
Table 2. Summary of clinical and radiological findings
Underlying disease
Angiographic findings
Calcified nodules
Continuous Filling Collateral flow of Size No. HTN DM CRF Hyperparathyroidism defect flow distal artery (mm) 1 2 3 4 5
+ − − − +
+ − − − +
− − − + −
− − − + −
+ + + + +
Good Good Poor Good Good
− − − + +
4.3 3.4 7.0 6.0 3.5
Shape Oval Oval Tubular Oval Round
Risk factor: source of calcified emboli
Carotid Aortic Cardiac artery arch valve + − + − +
+ − + + +
+ − + + +
Abbreviations: CRF, chronic renal failure; DM, diabetes mellitus; HTN, hypertension.
all patients showed small, dense single calcifications in the MCA with no definitive ischemic low-density lesions (M1: 3 and M2: 2). The mean size of calcified emboli was 4.3 mm (range 3.4-7.0 mm). Of the 5 patients, two were misdiagnosed as having parenchymal calcification by an experienced neuroradiologist. CT angiographies to evaluate stroke patients showed MCA obstructions by calcified emboli. The time from symptom onset to admission was 30240 minutes (median, 60 minutes) and the time from admission to femoral puncture was 30-90 minutes (median, 60 minutes). The median procedure time was 30 minutes (range, 25-35 minutes). Four patients received intravenous tissue plasminogen activator therapy before angiography. The initial mRS score at admission was 3-4 (median, 4). All patients had angiographic findings of filling defects from calcified emboli. Four patients had good collateral flow and two had continuous distal flow. All patients underwent MAT using a Penumbra reperfusion catheter as first-line therapy. However, MAT did not remove calcified emboli in all patients. CT images performed after cerebral angiography showed low-density infarctions in the MCA territory and no distal migration of calcified emboli. At discharge, the median NIHSS score was 4 (range, 2-15). Two patients with good collateral flow had favorable functional outcomes (mRS score ≤2). No hospital or 3-month mortality occurred. Potential embolic sources were identified using echocardiography, sonography, and CT angiography. Four patients had diffuse calcification in the aortic arch, carotid artery, and aortic valve. Of these patients, one had an ulcerated calcified nodule on carotid MRI and histopathological findings. One patient did not appear to have any calcified lesions on imaging studies.
Representative Case A 77-year-old man (patient 5) with dysarthria and rightsided weakness was admitted to our neurology department
via the emergency medical center. The onset-to-door time was 30 minutes. The NIHSS score was 4. The patient had a history of hypertension and had been taking medication for 20 years. The patient’s initial noncontrast brain CT scan showed a small calcified lesion of approximately 3.5 mm in the left M2 inferior division (Fig 1, A). Stroke MRI showed diffusion restriction and a low–ADCsignal lesion of the left MCA territory, consistent with acute cerebral infarction (Fig 1, B). Initial cerebral angiography showed a filling defect in the inferior branch of the left MCA with delayed distal flow (Fig 1, C). The microcatheter was introduced into the occlusion site of the left MCA and the Penumbra reperfusion catheter was advanced to the embolus. MAT failed because of the hardness of the calcified embolic material. After 2 days, carotid plaque MRI showed eccentric calcified thickening with intraplaque hemorrhage in the internal carotid artery (ICA) orifice and an unstable calcified nodule with a small ulcerative lesion in the left ICA orifice (Fig 1, D). No visible cardiac valve calcification was observed on transthoracic echocardiography. Cardiac CT angiogram showed diffuse atherosclerotic changes from the ascending aorta to the internal iliac artery. Carotid plaque MRI showed a calcified hemorrhagic plaque in the left ICA orifice. We presumed the calcified embolic source was from the left ICA orifice because calcified nodules in the left ICA orifice are unstable, ulcerative lesions. The patient underwent a left carotid endarterectomy. We found an ulcerative, hemorrhagic, calcified nodule on histopathological investigation.
Discussion We performed MAT in patients with calcified cerebral emboli on CT and cerebral angiography. However, MAT using a Penumbra reperfusion catheter did not result in the removal of calcified cerebral emboli in any patient. Two patients with good collateral flow had favorable functional outcomes (mRS score ≤2). Calcified cerebral embolus is an uncommon complication of calcified vascular diseases such as aortic plaques,
ARTICLE IN PRESS 4
E. KOH ET AL.
Figure 1. A 77-year-old man with a calcified cerebral embolus in an inferior branch of the left MCA. (A) Noncontrast brain CT scan showing an approximately 2-mm calcified lesion without brain parenchymal lesion (arrow). (B) Diffusion-weighted image showing diffusion restriction in the inferior division territory of the left MCA. (C) Cerebral angiography showing a filling defect in the inferior branch of the left MCA with delayed distal flow (arrow). (D) Axial image of time-of-flight MR angiography showing a calcified nodule in the left internal carotid artery orifice (arrow). Abbreviation: MCA, middle cerebral artery.
valvular calcification, or carotid plaques. Most patients have multiple calcifications in the cardiac valve, aortic arch, and carotid artery.2,4 Although migration of calcified plaque during heart catheterization, carotid artery manipulation, or cardiopulmonary resuscitation occurs in some patients, most cerebral events result from spontaneous
migration of calcified emboli.2,4 In our study, 4 patients (80%) had multiple calcified plaques and had acute ischemic strokes after spontaneous migration of calcified emboli. Spontaneous migration of cardiovascular calcification is probably due to ulceration and detachment of plaques under high blood pressure.3 In our study, 1 patient
ARTICLE IN PRESS ACUTE STROKE-RELATED CALCIFIED CEREBRAL EMBOLI
had an ulcerative, unstable calcified nodule in the ICA orifice. We identified the spontaneous migration of the calcified nodule with carotid plaque MRI and histopathological findings. Early recanalization following large-vessel occlusion is associated with improved clinical outcomes from acute ischemic stroke.9,10 MAT using a flexible aspiration catheter is an alternative method for opening blocked vessels.11-13 With the introduction of easily trackable and large aspiration catheters, recanalization rates and functional outcomes of MAT have become comparable to stentbased thrombectomy.14 Some studies report successful mechanical recanalization of calcified embolisms.15,16 In our study, MAT failed for all patients with calcified cerebral emboli because of hard emboli and packing of calcified emboli into the vessel lumen. The mean size of calcified emboli in the present study was 4.3 mm, which was larger than that in a previous study.2 We did not try stent-based thrombectomy because no microcatheter passage was available for stent deployment into the distal portion of occluded vessels. Walker et al2 reported the clinical outcomes for patients with calcified cerebral emboli. Residual neurological impairment from calcified emboli occurred in 33% of patients, complete neurological recovery was seen in 29%, and 16% died during initial hospitalization. Of 4 patients with good collateral flow in our study, two (50%) had favorable functional outcomes (mRS score ≤2). No hospital or 3-month mortality occurred. The recurrence rate for embolic infarction is 43% for patients with calcified emboli.2 Therefore, identifying embolic sources is important for determining appropriate treatment. However, in our study, most patients have multiple calcifications in the cardiovascular system. Therefore, surgical removal of all calcified plaques in the cardiovascular system is impossible. For patients with presumed embolic sources such as carotid calcified plaques, removal through carotid endarterectomy or carotid stenting is necessary. In conclusion, cerebral angiography supports a diagnosis of stroke when calcified cerebral emboli show contrast-filling defects, degrees of vascular occlusion, and collateral flow. However, in the present study, MAT in patients with calcified cerebral emboli was not an effective treatment because of hardness of calcified plaque and packing into the arterial lumen. These findings support the need for other options for recanalization of occluded vessels by calcified emboli in patients with acute ischemic stroke and workup of imaging studies to establish the presumed source of emboli.
5
References 1. Dandamudi VS, Thaler DE, Malek AM. Cerebral embolus following chiropractic manipulation in a patient with a calcified carotid artery. J Neuroimaging 2013;23:429-430. 2. Walker BS, Shah LM, Osborn AG. Calcified cerebral emboli, a “do not miss” imaging diagnosis. 22 new cases and review of the literature. AJNR Am J Neuroradiol 2014;35:1515-1519. 3. Rancurel G, Marelle L, Vincent D, et al. Spontaneous calcific cerebral embolus from a calcific aortic stenosis in a middle cerebral artery infarct. Stroke 1989;20:691-693. 4. Christian BA, Kirzeder DJ, Boyd J, et al. Showered calcific emboli to the brain, the “salted pretzel” sign, originating from the ipsilateral internal carotid artery causing acute cerebral infarction. Stroke 2009;40:e319-e321. 5. Kavanagh EC, Fenton DM, Heran MK, et al. Calcified cerebral emboli. AJNR Am J Neuroradiol 2006;27:19961999. 6. Okazaki S, Sakaguchi M, Sugiyama Y, et al. Ineffective thrombolytic therapy for calcified cerebral emboli originated from calcified internal carotid artery stenosis. Rinsho Shinkeigaku 2009;49:281-284. 7. Yoneyama T, Nakano S, Kawano H, et al. Combined direct percutaneous transluminal angioplasty and low-dose native tissue plasminogen activator therapy for acute embolic middle cerebral artery trunk occlusion. AJNR Am J Neuroradiol 2002;23:277-281. 8. Molina CA, Saver JL. Extending reperfusion therapy for acute ischemic stroke: emerging pharmacological, mechanical, and imaging strategies. Stroke 2005;36:23112320. 9. Rha JH, Saver JL. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke 2007;38:967-973. 10. Saver JL, Jahan R, Levy EI, et al. Solitaire flow restoration device versus the Merci Retriever in patients with acute ischemic stroke (SWIFT): a randomized, parallel-group, non-inferiority trial. Lancet 2012;380:1241-1249. 11. Kang DH, Hwang YH, Kim YS, et al. Direct thrombus retrieval using the reperfusion catheter of the penumbra system: forced-suction thrombectomy in acute ischemic stroke. AJNR Am J Neuroradiol 2011;32:283-287. 12. Jankowitz B, Aghaebrahim A, Zirra A, et al. Manual aspiration thrombectomy: adjunctive endovascular recanalization technique in acute stroke interventions. Stroke 2012;43:1408-1411. 13. Kim YS, Kwak HS, Chung GH, et al. Manual aspiration thrombectomy using the Penumbra catheter in patients with acute M1 occlusion: a single-center study. Interv Neuroradiol 2015;21:694-699. 14. Turk AS, Frei D, Fiorella D, et al. ADAPT FAST study: a direct aspiration first pass technique for acute stroke thrombectomy. J Neurointerv Surg 2014;6:260-264. 15. Fassa AA1, Mazighi M, Himbert D, et al. Successful endovascular stroke rescue with retrieval of an embolized calcium fragment after transcatheter aortic valve replacement. Circ Cardiovasc Interv 2014;7:125-126. 16. Ramírez-Moreno JM, Trinidad-Ruiz M, Ceberino D, et al. Mechanical thrombectomy during ischaemic stroke due to a calcified cerebral embolism. Neurología 2015;21:S213S4853.