- Email: [email protected]
A Dilated Surface Appearance on Basiparallel Anatomic Scanning–Magnetic Resonance Imaging Is a Useful Tool for the Diagnosis of Spontaneous Vertebral Artery Dissection in Lateral Medullary Infarction
A Dilated Surface Appearance on Basiparallel Anatomic Scanning–Magnetic Resonance Imaging Is a Useful Tool for the Diagnosis of Spontaneous Vertebral Artery Dissection in Lateral Medullary Infarction Ryo Itabashi, MD,*† Etsuro Mori, MD, PhD,† Eisuke Furui, MD, PhD,* Shoichiro Sato, MD, PhD,* Yukako Yazawa, MD,* Kenta Kawata, MD,* and Satoru Fujiwara, MD, PhD‡
Spontaneous dissection of the vertebral artery (VA) is a major vascular lesion causing lateral medullary infarction (LMI). A dilated surface appearance of the VA is a feature of VA dissection and can be observed on basiparallel anatomic scanning (BPAS)–magnetic resonance imaging (MRI). The aim of this study was to validate BPAS-MRI in the diagnosis of VA dissection in patients with LMI. The subjects of the present study were 41 consecutive patients with LMI within 7 days of onset. The diagnosis of VA dissection was made with the clinical criteria-based diagnosis. Percent (%) dilatation of the VA on BPAS-MRI was calculated by comparing the maximum surface diameter of the intracranial VA to the diameter of the distal normal surface of the VA. Fourteen patients (34%) were diagnosed with VA dissection. The optimal cutoff % dilatation of the VA for dissection was more than 169%. The sensitivity and specificity of % dilatation of VA more than 169% and aneurysmal dilatation, stenosis, or occlusion on magnetic resonance angiography (MRA) for VA dissection were 92.9% and 81.5%, respectively. BPAS-MRI combined with time-offlight–MRA is a useful tool for the diagnosis of VA dissection in patients with acute LMI. Key Words: Acute stroke—lateral medullary infarction—vertebral artery— dissection—magnetic resonance imaging—magnetic resonance angiography. Ó 2013 by National Stroke Association
Introduction
From the *Department of Stroke Neurology, Kohnan Hospital, Sendai; †Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Miyagi; and ‡Department of Neurosurgery, Kohnan Hospital, Sendai, Japan. Received May 15, 2013; revision received June 20, 2013; accepted July 5, 2013. Disclosures: The authors report no conflicts of interest. Sources of funding: None. Address correspondence to Ryo Itabashi, MD, Department of Stroke Neurology, Kohnan Hospital, 4-20-1 Nagamachiminami, Taihaku-ku, Sendai 982-8523, Japan. E-mail: ritabash@ kohnan-sendai.or.jp. 1052-3057/$ - see front matter Ó 2013 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.07.003
In Japan, the most common site of cervicocephalic arterial dissection is the intracranial vertebral artery (VA), according to a retrospective, multicenter, registration study (the Spontaneous Cervicocephalic Arterial Dissections Study [SCADS]),1 whereas both the extracranial carotid and vertebral arteries are equally involved in Western countries.2 VA dissection is the second most common cause of lateral medullary infarction (LMI) (14%-33%) after atherothrombosis of the VA or posterior inferior cerebellar artery.3,4 Although dilatation of the outer wall of the VA is a feature of VA dissection associated with aneurysmal formation, regular magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) usually fail to demonstrate it because of the effect of blood flow or thrombus.
Journal of Stroke and Cerebrovascular Diseases, Vol. -, No. - (---), 2013: pp 1-6
1
R. ITABASHI ET AL.
2 5
Nagahata et al modified the surface anatomic scanning– MRI technique and developed basiparallel anatomic scanning (BPAS)–MRI to observe the surface appearance of the intracranial vertebrobasilar artery. BPAS-MRI demonstrates the outer contour of the vertebrobasilar artery free from the effect of flow or thrombus. Because a dilated surface appearance of the VA with vessel stenosis on MRA has been described in a case report of LMI caused by VA dissection,6 BPAS-MRI is a promising tool for screening for VA dissection in LMI patients.7 However, the value of BPAS-MRI has not been determined in the diagnosis of LMI. The aim of the present study was to validate BPAS-MRI in the diagnosis of spontaneous VA dissection in patients with LMI.
Methods Study Population The subjects of the present study were 41 consecutive patients (60.6 6 15.0 years old, 30 men) with acute LMI who were admitted to Kohnan Hospital Stroke Center (Sendai, Japan) between August 2006 and December 2012. All patients with acute stroke admitted to the center during this period were examined by neurologists, neurosurgeons, or both and screened by routine laboratory tests and computed tomography (CT) or MRI. Ischemic stroke was diagnosed by vascular neurologists (board-certified neurologists specializing in the care of stroke patients) based on the clinical and brain imaging findings. The clinical and investigative data, thus, prospectively collected in a standardized fashion were entered into the Kohnan Hospital Stroke Registry, in which 2950 patients with ischemic stroke were identified. The inclusion criteria for the present study were acute (within 7 days after onset) isolated LMI verified on MRI with diffusion-weighted imaging (DWI) during the hospital stay and at least one of the following acute neurological symptoms/signs because of LMI: limb ataxia, lateropulsion, Horner syndrome, dysphagia, and sensory disturbance. LMI associated with other VA territory infarcts were not included. Other exclusion criteria were histories of head trauma, coagulopathy, and cerebral angiitis.
the craniocaudal direction. BPAS-MRI was performed in a 20-mm-thick coronal section parallel to the clivus using the fast spin-echo sequence. The following imaging parameters were used: TR 5000 ms, TE 760 ms, field of view 160 3 160 mm, 384 3 224 matrix. Acquisition time was 25 seconds. Gray-scale reversal was added in the postprocessing. The dilated appearance of the ipsilateral VA was viewed on the BPAS-MRI. When obtained on multiple occasions, the most dilated image during the hospital stay was used. Percent (%) dilatation of the VA was measured as % dilatation 5 Ddilatation/Dnormal 3 100, where Ddilatation 5 the maximum diameter of the intracranial surface of the ipsilateral VA and Dnormal 5 the diameter of the distal ipsilateral VA at its non-tortuous normal segment on BPAS-MRI (Fig 1). Using a hand-held digital caliper, 1 investigator (R.I.), who was unaware of all clinical data, measured Ddilatation and Dnormal on BPAS-MRI. We addressed test–retest reliability of this method on randomly selected 20 patients. Intraclass correlation coefficient was .774 (95% confidence interval [CI]: .52-.90). We adopted the data from the first measurement for the analyses. MRA performed simultaneously with BPAS-MRI was also reviewed, especially about aneurysmal dilatation, stenosis (presence of 50%-99% atherosclerotic stenosis using a method similar to the WASID method8), or occlusion of the ipsilateral VA.
Etiological Diagnosis The diagnosis of VA dissection was made when 1 or more SCADS major criteria were present1,9: (1) ‘‘double
MRI Study DWI, BPAS-MRI, and time-of-flight (TOF)–MRA were performed at least once during the hospital stay with a 1.5-T unit (SIGNA EXCITE; GE Medical Systems, Milwaukee, WI). DWI was obtained using echo-planar imaging with bmax 5 1000 s/mm2, repetition time (TR) 8000 ms, echo time (TE) 76.3 ms, and field of view 18 3 18 mm. Cranial MRA was obtained using a 3-dimensional (3D) TOF technique. Imaging parameters were TR 29 ms, TE 6.9 ms, 20 flip angle, field of view 160 3 160 mm, 256 3 128 matrix, and 129 sections with a 1.2-mm effective thickness that resulted in the coverage of a volume of 77 mm in
Figure 1. % Dilatation of the VA on BPAS-MRI (% dilatation 5 Ddilatation/Dnormal 3 100). Abbreviations: BPAS, basiparallel anatomic scanning; MRI, magnetic resonance imaging; VA, vertebral artery.
BPAS-MRI FOR THE DIAGNOSIS OF SPONTANEOUS VA DISSECTION IN LMI
3
Table 1. Consecutive LMI patients diagnosed as having VA dissection
No.
Age
Gender
SCADS major criteria
BPAS time from onset (days)
% VA dilatation
Findings of TOF-MRA
1 2 3 4 5* 6 7 8 9 10 11 12 13 14
32 46 59 41 54 46 55 39 54 57 43 39 72 29
Male Male Male Male Male Male Male Male Male Female Female Male Female Male
1 1 1, 2 2 1 1 1, 2 1 2 1 1 1 1 1
9 0 6 5 1 0 2 0 1 3 0 4 6 0
264 184 230 200 164 306 169 292 182 309 170 171 609 177
Aneurysmal dilatation and stenosis Stenosis Stenosis Stenosis Stenosis Aneurysmal dilatation and stenosis Stenosis Aneurysmal dilatation Stenosis Occlusion Stenosis Aneurysmal dilatation Aneurysmal dilatation Stenosis
Abbreviations: BPAS, basiparallel anatomic scanning; MRA, magnetic resonance angiography; SCAD, Spontaneous Cervicocephalic Arterial Dissections Study; TOF, time-of-flight; VA, vertebral artery. *Pseudonegative patients of dilated appearance of VA on BPAS-MRI.
lumen’’ or ‘‘intimal flap’’ demonstrated on at least one of digital subtraction angiography (DSA), MRI, MRA, computed tomographic angiography (CTA), or duplex ultrasonography; (2) ‘‘pearl and string sign’’ or ‘‘string sign’’ demonstrated on DSA; and (3) pathological confirmation of arterial dissection. The other stroke subtypes were classified into modifications of the previous criteria3,10: (1) Large-artery atherosclerosis: (a) patients with brain imaging findings of either significant (.50%) stenosis or occlusion of the ipsilateral VA, presumably because of atherosclerosis, and (b) patients without a potential source of cardioembolism; (2) Cardioembolism: (a) patients with concurrent cardiac source for an embolus (atrial fibrillation, segmental wall akinesis, cardiomyopathy, or right to left shunt with deep venous thrombosis or pulmonary thromboembolism) and (b) patients without VA stenosis of greater than 50%; (3) Small-artery occlusion: (a) patients with isolated small infarct with a diameter of less than 1.5 cm and (b) patients without a cardiac source for an embolus or VA stenosis of greater than 50%; and (4) Other causes: (a) patients who did not undergo sufficient examinations for etiological diagnosis and (b) ambiguous cases such as those with embolic heart disease and severe VA stenosis.
with and without VA dissection. To obtain the optimal cutoff of % dilatation of VA as the cutoff point for discriminating between patients with VA dissection and those without, receiver operating characteristic curves were constructed, and the areas under the curve with 95% CIs were calculated. Finally, the sensitivity and specificity of VA dilatation on BPAS-MRI for VA dissection were calculated. An alpha of .05 (2 sided) was considered a significant difference in all analyses.
Results Fourteen patients (34.2%) were diagnosed as having spontaneous VA dissection according to the SCADS major
Analysis Statistical analyses were done with the JMP (SAS Institute Inc., Cary, NC) statistical software package. The c2 test and the Kruskal–Wallis test were used, as appropriate, to compare clinical characteristics between patients
Figure 2. Receiver operating characteristic curves to show the optimal cutoff point of % dilatation of the VA to predict VA dissection.
R. ITABASHI ET AL.
4
Figure 3. A 41-year-old man (dissection case no. 4) was brought to our department 3 hours after onset because of right neck pain and right Wallenberg syndrome. On admission, DWI shows acute right LMI. (A) BPAS-MRI shows a dilated surface of the VA (white arrow) 5 days after onset; % dilatation is 200%. (B) TOF-MRA shows a pearl and string sign on the right VA (black arrow). (C) SPGR images show a double lumen in the right VA (white arrowhead). Abbreviations: BPAS, basiparallel anatomic scanning; DWI, diffusion-weighted imaging; LMI, lateral medullary infarction; MRA, magnetic resonance angiography; SPGR, spoiled gradient–recalled acquisition in the steady state; TOF, time-offlight; VA, vertebral artery.
criteria. The clinical and neuroradiological characteristics of patients with spontaneous VA dissection are summarized in Table 1. In addition to MRA, the following vascular imaging examinations were performed: duplex ultrasonography in 37 patients, DSA in 9 patients, and CTA in 2 patients. In the other 27 patients, 14 were diagnosed as having large-artery atherosclerosis, 11 as having small-artery occlusion, and 2 as having other causes. The median time from onset to BPAS-MRI was 1 day (interquartile range, .5-4); % dilatation of the VA was
significantly higher in patients with VA dissection than in those without dissection (192% vs. 160%, P 5 .0009). According to the areas under the curve of the receiver operating characteristic curve for predicting VA dissection, the optimal cutoff % dilatation of the VA was more than 169%, with a sensitivity of 92.9% (95% CI: 66.1%-99.8%) and a specificity of 66.7% (46.0%-83.5%) (Fig 2). An illustrative case of VA dissection with surface dilatation of the VA on BPAS-MRI is presented in Figure 3, A-C. Twenty-seven patients (65.9%) had abnormal findings (2 aneurysmal dilatation and stenosis, 3 aneurysmal dilatation, 11 stenosis, and 11 occlusion) on TOF-MRA. The
Table 2. The sensitivity and specificity of dilated appearance of VA on BPAS-MRI and TOF-MRA for VA dissection Findings on BPAS-MRI or TOF-MRA
Sensitivity (95% CI)
Specificity (95% CI)
% Dilatation of VA .169% Aneurysmal dilatation, stenosis, or occlusion on TOF-MRA % Dilatation of VA .169% and aneurysmal dilatation, stenosis, or occlusion on TOF-MRA
92.9% (66.1%-99.8%) 100% (80.7%-100%)
66.7% (46.0%-83.5%) 51.9% (32.0%-71.3 %)
92.9% (66.1%-99.8%)
85.2% (61.9%-93.7%)
Abbreviations: BPAS, basiparallel anatomic scanning; CI, confidence interval; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; TOF, time-of-flight; VA, vertebral artery.
BPAS-MRI FOR THE DIAGNOSIS OF SPONTANEOUS VA DISSECTION IN LMI
5
Figure 4. A 64-year-old man with hypertension was brought to our department because of limb ataxia and dysarthria. (A) Three days after onset, BPAS-MRI shows a dilated surface of the VA (white arrow); % dilatation is 206%. (B) TOF-MRA shows complete occlusion of the left VA (black arrow). Repeated vascular imaging examinations (MRA with contrast medium and DSA) show neither a lumen nor an intimal flap. The final diagnosis was large-artery atherosclerosis. Abbreviations: BPAS, basiparallel anatomic scanning; DSA, digital subtraction angiography; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; TOF, time-offlight; VA, vertebral artery.
sensitivity and specificity of aneurysmal dilatation, stenosis, or occlusion on TOF-MRA for VA dissection were 100% and 51.9%, respectively. The combination of % dilatation of the VA more than 169% and these abnormal findings on TOF-MRA provided a high sensitivity and specificity for predicting VA dissection, 92.9% and 85.2%, respectively (Table 2). One patient without % dilatation of VA more than 169% were diagnosed as having VA dissection (pseudonegative) and 4 patients with % dilatation of VA more than 169% were diagnosed as not having dissection (pseudopositive). Of the 4 pseudopositives, 3 showed complete occlusion of the VA on TOF-MRA. A typical pseudopositive case is presented in Figure 4.
Discussion Intracranial artery dissection is known to cause subarachnoid hemorrhage because the main dissection plane is located in the subadventitia.11 Yamada et al12 reported a patient with ischemia caused by unrecognized intracranial dissection who developed a subarachnoid hemorrhage during antithrombotic therapy. Therefore, early detection of VA dissection with high sensitivity is required for the management of acute LMI. Conventional DSA, 3D TOF-MRA, contrast-enhanced 3D imaging with spoiled gradient–recalled acquisition in the steady state sequence (SPGR), and CTA have been used in the diagnosis of VA dissection. DSA has long been the criterion standard for the diagnosis or follow-up of VA dissection.13 However, this technique is not without risk. Previous studies have shown the usefulness of 3D TOF-MRA combined with MRI for the detection of VA dissection.14,15 The sensitivity and specificity are reportedly 20% and 100% for MRI and 60% and 98% for MRA.14 The sensitivity, specificity, accuracy, and positive and negative predictive values of multisectional CTA for diagnosing VA dissection were reported to be 100%, 98%, 98.5%,
95%, and 100%, respectively,16 but CTA requires contrast medium. The present study is the first to demonstrate a significant association between a dilated appearance of the VA on BPAS-MRI and VA dissection. BPAS-MRI was useful to detect VA dissection in patients with LMI. Aneurysmal formation or intramural hematoma caused by disruption of the internal elastic lamina could be depicted as surface dilatation of dissecting arteries.17 BPAS-MRI illustrates the outer contour of the vertebrobasilar artery, free from the influence of flow or thrombus, whereas other established imaging modalities, such as MRA or DSA, show the inner contour of the vessels.5 Furthermore, the procedure of BPAS-MRI is very simple, requiring about 1 minute, and available with most MRI machines. In patients who have a dilated surface appearance of the VA and aneurysmal dilatation, stenosis, or occlusion, additional imaging, such as multisectional CTA, SPGR–MRI, and DSA, should be considered to confirm the diagnosis of VA dissection. When the optimal cutoff is applied, the sensitivity and specificity of BPAS-MRI may not be sufficiently high. The low sensitivity might be because of inappropriate timing of BPAS-MRI. In pseudonegative case, the timing of BPAS-MRI might be too late for evaluation of appropriate surface dilatation of the VA. Images without a dilated VA surface could be caused by regression of the surface dilatation in acute VA dissection. Repeated imaging might improve the sensitivity of this method. The low specificity can be explained by dilatation of the vessel not because of dissection but vascular remodeling caused by atherosclerotic change. Of the 4 pseudopositive patients, 3 showed complete occlusion of the VA on TOF-MRA. If additional imaging could not reveal a double lumen or intimal flap, such cases would be diagnosed as largeartery atherosclerosis. However, because the present study is based primarily on neuroradiological factors, there is no denying the possibility that the criteriabased diagnosis overlooked true dissection. Although
R. ITABASHI ET AL.
6
there were no patients with extracranial VA dissection in the present LMI series, BPAS-MRI is useless for evaluating the extracranial VA, which is another drawback of BPAS-MRI. In any event, because of its simplicity and safety, we believe that BPAS-MRI is a useful tool for the diagnosis of spontaneous VA dissection in patients with acute LMI.
References 1. Minematsu K, Matsuoka H, Kasuya J. Cervicocephalic arterial dissection in Japan: analysis of 454 patients in the spontaneous cervicocephalic arterial dissection study I (SCADS-I) (abstract). Stroke 2008;39:566. 2. Caplan LR. Dissections of brain-supplying arteries. Nat Clin Pract Neurol 2008;4:34-42. 3. Kim JS. Pure lateral medullary infarction: clinicalradiological correlation of 130 acute, consecutive patients. Brain 2003;126:1864-1872. 4. Hosoya T, Watanabe N, Yamaguchi K, et al. Intracranial vertebral artery dissection in Wallenberg syndrome. AJNR Am J Neuroradiol 1994;15:1161-1165. 5. Nagahata M, Abe Y, Ono S, et al. Surface appearance of the vertebrobasilar artery revealed on basiparallel anatomic scanning (BPAS)-MR imaging: its role for brain MR examination. AJNR Am J Neuroradiol 2005; 26:2508-2513. 6. Hamaguchi T, Yamada M. Basiparallel anatomic scanning-magnetic resonance imaging in vertebral artery dissection. Arch Neurol 2009;66:276-277. 7. Takemoto K, Takano K, Abe H, et al. The new MRI modalities ‘‘BPAS and VISTA’’ for the diagnosis of VA dissection. Acta Neurochir Suppl 2011;112:59-65.
8. Samuels OB, Joseph GJ, Lynn MJ, et al. A standardized method for measuring intracranial arterial stenosis. AJNR Am J Neuroradiol 2000;21:643-646. 9. Sato S, Toyoda K, Matsuoka H, et al. Isolated anterior cerebral artery territory infarction: dissection as an etiological mechanism. Cerebrovasc Dis 2010;29:170-177. 10. Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. TOAST: Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24: 35-41. 11. Pelkonen O, Tikkakoski T, Pyhtinen J, et al. Cerebral CT and MRI findings in cervicocephalic artery dissection. Acta Radiol 2004;45:259-265. 12. Yamada SM, Nakane M, Aoki M, et al. Dissecting aneurysm of the anterior cerebral artery with severe subarachnoid hemorrhage during treatment for cerebral infarction. Int Med 2003;42:433-435. 13. Mokri B, Houser OW, Sandok BA, et al. Spontaneous dissections of the vertebral arteries. Neurology 1988; 38:880-885. 14. Levy C, Laissy JP, Raveau V, et al. Carotid and vertebral artery dissections: three-dimensional time-of-flight MR angiography and MR imaging versus conventional angiography. Radiology 1994;190:97-103. 15. Mascalchi M, Bianchi MC, Mangiafico S, et al. MRI and MR angiography of vertebral artery dissection. Neuroradiology 1997;39:329-340. 16. Chen CJ, Tseng YC, Lee TH, et al. Multisection CT angiography compared with catheter angiography in diagnosing vertebral dissection. AJNR Am J Neuroradiol 2004; 25:769-774. 17. Mizutani T, Kojima H, Asamoto S, et al. Pathological mechanism and three-dimensional structure of cerebral dissecting aneurysms. J Neurosurg 2001;94:712-717.
Spontaneous dissection of the vertebral artery (VA) is a major vascular lesion causing lateral medullary infarction (LMI). A dilated surface appearance of the VA is a feature of VA dissection and can be observed on basiparallel anatomic scanning (BPAS)–magnetic resonance imaging (MRI). The aim of this study was to validate BPAS-MRI in the diagnosis of VA dissection in patients with LMI. The subjects of the present study were 41 consecutive patients with LMI within 7 days of onset. The diagnosis of VA dissection was made with the clinical criteria-based diagnosis. Percent (%) dilatation of the VA on BPAS-MRI was calculated by comparing the maximum surface diameter of the intracranial VA to the diameter of the distal normal surface of the VA. Fourteen patients (34%) were diagnosed with VA dissection. The optimal cutoff % dilatation of the VA for dissection was more than 169%. The sensitivity and specificity of % dilatation of VA more than 169% and aneurysmal dilatation, stenosis, or occlusion on magnetic resonance angiography (MRA) for VA dissection were 92.9% and 81.5%, respectively. BPAS-MRI combined with time-offlight–MRA is a useful tool for the diagnosis of VA dissection in patients with acute LMI. Key Words: Acute stroke—lateral medullary infarction—vertebral artery— dissection—magnetic resonance imaging—magnetic resonance angiography. Ó 2013 by National Stroke Association
Introduction
From the *Department of Stroke Neurology, Kohnan Hospital, Sendai; †Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, Sendai, Miyagi; and ‡Department of Neurosurgery, Kohnan Hospital, Sendai, Japan. Received May 15, 2013; revision received June 20, 2013; accepted July 5, 2013. Disclosures: The authors report no conflicts of interest. Sources of funding: None. Address correspondence to Ryo Itabashi, MD, Department of Stroke Neurology, Kohnan Hospital, 4-20-1 Nagamachiminami, Taihaku-ku, Sendai 982-8523, Japan. E-mail: ritabash@ kohnan-sendai.or.jp. 1052-3057/$ - see front matter Ó 2013 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.07.003
In Japan, the most common site of cervicocephalic arterial dissection is the intracranial vertebral artery (VA), according to a retrospective, multicenter, registration study (the Spontaneous Cervicocephalic Arterial Dissections Study [SCADS]),1 whereas both the extracranial carotid and vertebral arteries are equally involved in Western countries.2 VA dissection is the second most common cause of lateral medullary infarction (LMI) (14%-33%) after atherothrombosis of the VA or posterior inferior cerebellar artery.3,4 Although dilatation of the outer wall of the VA is a feature of VA dissection associated with aneurysmal formation, regular magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) usually fail to demonstrate it because of the effect of blood flow or thrombus.
Journal of Stroke and Cerebrovascular Diseases, Vol. -, No. - (---), 2013: pp 1-6
1
R. ITABASHI ET AL.
2 5
Nagahata et al modified the surface anatomic scanning– MRI technique and developed basiparallel anatomic scanning (BPAS)–MRI to observe the surface appearance of the intracranial vertebrobasilar artery. BPAS-MRI demonstrates the outer contour of the vertebrobasilar artery free from the effect of flow or thrombus. Because a dilated surface appearance of the VA with vessel stenosis on MRA has been described in a case report of LMI caused by VA dissection,6 BPAS-MRI is a promising tool for screening for VA dissection in LMI patients.7 However, the value of BPAS-MRI has not been determined in the diagnosis of LMI. The aim of the present study was to validate BPAS-MRI in the diagnosis of spontaneous VA dissection in patients with LMI.
Methods Study Population The subjects of the present study were 41 consecutive patients (60.6 6 15.0 years old, 30 men) with acute LMI who were admitted to Kohnan Hospital Stroke Center (Sendai, Japan) between August 2006 and December 2012. All patients with acute stroke admitted to the center during this period were examined by neurologists, neurosurgeons, or both and screened by routine laboratory tests and computed tomography (CT) or MRI. Ischemic stroke was diagnosed by vascular neurologists (board-certified neurologists specializing in the care of stroke patients) based on the clinical and brain imaging findings. The clinical and investigative data, thus, prospectively collected in a standardized fashion were entered into the Kohnan Hospital Stroke Registry, in which 2950 patients with ischemic stroke were identified. The inclusion criteria for the present study were acute (within 7 days after onset) isolated LMI verified on MRI with diffusion-weighted imaging (DWI) during the hospital stay and at least one of the following acute neurological symptoms/signs because of LMI: limb ataxia, lateropulsion, Horner syndrome, dysphagia, and sensory disturbance. LMI associated with other VA territory infarcts were not included. Other exclusion criteria were histories of head trauma, coagulopathy, and cerebral angiitis.
the craniocaudal direction. BPAS-MRI was performed in a 20-mm-thick coronal section parallel to the clivus using the fast spin-echo sequence. The following imaging parameters were used: TR 5000 ms, TE 760 ms, field of view 160 3 160 mm, 384 3 224 matrix. Acquisition time was 25 seconds. Gray-scale reversal was added in the postprocessing. The dilated appearance of the ipsilateral VA was viewed on the BPAS-MRI. When obtained on multiple occasions, the most dilated image during the hospital stay was used. Percent (%) dilatation of the VA was measured as % dilatation 5 Ddilatation/Dnormal 3 100, where Ddilatation 5 the maximum diameter of the intracranial surface of the ipsilateral VA and Dnormal 5 the diameter of the distal ipsilateral VA at its non-tortuous normal segment on BPAS-MRI (Fig 1). Using a hand-held digital caliper, 1 investigator (R.I.), who was unaware of all clinical data, measured Ddilatation and Dnormal on BPAS-MRI. We addressed test–retest reliability of this method on randomly selected 20 patients. Intraclass correlation coefficient was .774 (95% confidence interval [CI]: .52-.90). We adopted the data from the first measurement for the analyses. MRA performed simultaneously with BPAS-MRI was also reviewed, especially about aneurysmal dilatation, stenosis (presence of 50%-99% atherosclerotic stenosis using a method similar to the WASID method8), or occlusion of the ipsilateral VA.
Etiological Diagnosis The diagnosis of VA dissection was made when 1 or more SCADS major criteria were present1,9: (1) ‘‘double
MRI Study DWI, BPAS-MRI, and time-of-flight (TOF)–MRA were performed at least once during the hospital stay with a 1.5-T unit (SIGNA EXCITE; GE Medical Systems, Milwaukee, WI). DWI was obtained using echo-planar imaging with bmax 5 1000 s/mm2, repetition time (TR) 8000 ms, echo time (TE) 76.3 ms, and field of view 18 3 18 mm. Cranial MRA was obtained using a 3-dimensional (3D) TOF technique. Imaging parameters were TR 29 ms, TE 6.9 ms, 20 flip angle, field of view 160 3 160 mm, 256 3 128 matrix, and 129 sections with a 1.2-mm effective thickness that resulted in the coverage of a volume of 77 mm in
Figure 1. % Dilatation of the VA on BPAS-MRI (% dilatation 5 Ddilatation/Dnormal 3 100). Abbreviations: BPAS, basiparallel anatomic scanning; MRI, magnetic resonance imaging; VA, vertebral artery.
BPAS-MRI FOR THE DIAGNOSIS OF SPONTANEOUS VA DISSECTION IN LMI
3
Table 1. Consecutive LMI patients diagnosed as having VA dissection
No.
Age
Gender
SCADS major criteria
BPAS time from onset (days)
% VA dilatation
Findings of TOF-MRA
1 2 3 4 5* 6 7 8 9 10 11 12 13 14
32 46 59 41 54 46 55 39 54 57 43 39 72 29
Male Male Male Male Male Male Male Male Male Female Female Male Female Male
1 1 1, 2 2 1 1 1, 2 1 2 1 1 1 1 1
9 0 6 5 1 0 2 0 1 3 0 4 6 0
264 184 230 200 164 306 169 292 182 309 170 171 609 177
Aneurysmal dilatation and stenosis Stenosis Stenosis Stenosis Stenosis Aneurysmal dilatation and stenosis Stenosis Aneurysmal dilatation Stenosis Occlusion Stenosis Aneurysmal dilatation Aneurysmal dilatation Stenosis
Abbreviations: BPAS, basiparallel anatomic scanning; MRA, magnetic resonance angiography; SCAD, Spontaneous Cervicocephalic Arterial Dissections Study; TOF, time-of-flight; VA, vertebral artery. *Pseudonegative patients of dilated appearance of VA on BPAS-MRI.
lumen’’ or ‘‘intimal flap’’ demonstrated on at least one of digital subtraction angiography (DSA), MRI, MRA, computed tomographic angiography (CTA), or duplex ultrasonography; (2) ‘‘pearl and string sign’’ or ‘‘string sign’’ demonstrated on DSA; and (3) pathological confirmation of arterial dissection. The other stroke subtypes were classified into modifications of the previous criteria3,10: (1) Large-artery atherosclerosis: (a) patients with brain imaging findings of either significant (.50%) stenosis or occlusion of the ipsilateral VA, presumably because of atherosclerosis, and (b) patients without a potential source of cardioembolism; (2) Cardioembolism: (a) patients with concurrent cardiac source for an embolus (atrial fibrillation, segmental wall akinesis, cardiomyopathy, or right to left shunt with deep venous thrombosis or pulmonary thromboembolism) and (b) patients without VA stenosis of greater than 50%; (3) Small-artery occlusion: (a) patients with isolated small infarct with a diameter of less than 1.5 cm and (b) patients without a cardiac source for an embolus or VA stenosis of greater than 50%; and (4) Other causes: (a) patients who did not undergo sufficient examinations for etiological diagnosis and (b) ambiguous cases such as those with embolic heart disease and severe VA stenosis.
with and without VA dissection. To obtain the optimal cutoff of % dilatation of VA as the cutoff point for discriminating between patients with VA dissection and those without, receiver operating characteristic curves were constructed, and the areas under the curve with 95% CIs were calculated. Finally, the sensitivity and specificity of VA dilatation on BPAS-MRI for VA dissection were calculated. An alpha of .05 (2 sided) was considered a significant difference in all analyses.
Results Fourteen patients (34.2%) were diagnosed as having spontaneous VA dissection according to the SCADS major
Analysis Statistical analyses were done with the JMP (SAS Institute Inc., Cary, NC) statistical software package. The c2 test and the Kruskal–Wallis test were used, as appropriate, to compare clinical characteristics between patients
Figure 2. Receiver operating characteristic curves to show the optimal cutoff point of % dilatation of the VA to predict VA dissection.
R. ITABASHI ET AL.
4
Figure 3. A 41-year-old man (dissection case no. 4) was brought to our department 3 hours after onset because of right neck pain and right Wallenberg syndrome. On admission, DWI shows acute right LMI. (A) BPAS-MRI shows a dilated surface of the VA (white arrow) 5 days after onset; % dilatation is 200%. (B) TOF-MRA shows a pearl and string sign on the right VA (black arrow). (C) SPGR images show a double lumen in the right VA (white arrowhead). Abbreviations: BPAS, basiparallel anatomic scanning; DWI, diffusion-weighted imaging; LMI, lateral medullary infarction; MRA, magnetic resonance angiography; SPGR, spoiled gradient–recalled acquisition in the steady state; TOF, time-offlight; VA, vertebral artery.
criteria. The clinical and neuroradiological characteristics of patients with spontaneous VA dissection are summarized in Table 1. In addition to MRA, the following vascular imaging examinations were performed: duplex ultrasonography in 37 patients, DSA in 9 patients, and CTA in 2 patients. In the other 27 patients, 14 were diagnosed as having large-artery atherosclerosis, 11 as having small-artery occlusion, and 2 as having other causes. The median time from onset to BPAS-MRI was 1 day (interquartile range, .5-4); % dilatation of the VA was
significantly higher in patients with VA dissection than in those without dissection (192% vs. 160%, P 5 .0009). According to the areas under the curve of the receiver operating characteristic curve for predicting VA dissection, the optimal cutoff % dilatation of the VA was more than 169%, with a sensitivity of 92.9% (95% CI: 66.1%-99.8%) and a specificity of 66.7% (46.0%-83.5%) (Fig 2). An illustrative case of VA dissection with surface dilatation of the VA on BPAS-MRI is presented in Figure 3, A-C. Twenty-seven patients (65.9%) had abnormal findings (2 aneurysmal dilatation and stenosis, 3 aneurysmal dilatation, 11 stenosis, and 11 occlusion) on TOF-MRA. The
Table 2. The sensitivity and specificity of dilated appearance of VA on BPAS-MRI and TOF-MRA for VA dissection Findings on BPAS-MRI or TOF-MRA
Sensitivity (95% CI)
Specificity (95% CI)
% Dilatation of VA .169% Aneurysmal dilatation, stenosis, or occlusion on TOF-MRA % Dilatation of VA .169% and aneurysmal dilatation, stenosis, or occlusion on TOF-MRA
92.9% (66.1%-99.8%) 100% (80.7%-100%)
66.7% (46.0%-83.5%) 51.9% (32.0%-71.3 %)
92.9% (66.1%-99.8%)
85.2% (61.9%-93.7%)
Abbreviations: BPAS, basiparallel anatomic scanning; CI, confidence interval; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; TOF, time-of-flight; VA, vertebral artery.
BPAS-MRI FOR THE DIAGNOSIS OF SPONTANEOUS VA DISSECTION IN LMI
5
Figure 4. A 64-year-old man with hypertension was brought to our department because of limb ataxia and dysarthria. (A) Three days after onset, BPAS-MRI shows a dilated surface of the VA (white arrow); % dilatation is 206%. (B) TOF-MRA shows complete occlusion of the left VA (black arrow). Repeated vascular imaging examinations (MRA with contrast medium and DSA) show neither a lumen nor an intimal flap. The final diagnosis was large-artery atherosclerosis. Abbreviations: BPAS, basiparallel anatomic scanning; DSA, digital subtraction angiography; MRA, magnetic resonance angiography; MRI, magnetic resonance imaging; TOF, time-offlight; VA, vertebral artery.
sensitivity and specificity of aneurysmal dilatation, stenosis, or occlusion on TOF-MRA for VA dissection were 100% and 51.9%, respectively. The combination of % dilatation of the VA more than 169% and these abnormal findings on TOF-MRA provided a high sensitivity and specificity for predicting VA dissection, 92.9% and 85.2%, respectively (Table 2). One patient without % dilatation of VA more than 169% were diagnosed as having VA dissection (pseudonegative) and 4 patients with % dilatation of VA more than 169% were diagnosed as not having dissection (pseudopositive). Of the 4 pseudopositives, 3 showed complete occlusion of the VA on TOF-MRA. A typical pseudopositive case is presented in Figure 4.
Discussion Intracranial artery dissection is known to cause subarachnoid hemorrhage because the main dissection plane is located in the subadventitia.11 Yamada et al12 reported a patient with ischemia caused by unrecognized intracranial dissection who developed a subarachnoid hemorrhage during antithrombotic therapy. Therefore, early detection of VA dissection with high sensitivity is required for the management of acute LMI. Conventional DSA, 3D TOF-MRA, contrast-enhanced 3D imaging with spoiled gradient–recalled acquisition in the steady state sequence (SPGR), and CTA have been used in the diagnosis of VA dissection. DSA has long been the criterion standard for the diagnosis or follow-up of VA dissection.13 However, this technique is not without risk. Previous studies have shown the usefulness of 3D TOF-MRA combined with MRI for the detection of VA dissection.14,15 The sensitivity and specificity are reportedly 20% and 100% for MRI and 60% and 98% for MRA.14 The sensitivity, specificity, accuracy, and positive and negative predictive values of multisectional CTA for diagnosing VA dissection were reported to be 100%, 98%, 98.5%,
95%, and 100%, respectively,16 but CTA requires contrast medium. The present study is the first to demonstrate a significant association between a dilated appearance of the VA on BPAS-MRI and VA dissection. BPAS-MRI was useful to detect VA dissection in patients with LMI. Aneurysmal formation or intramural hematoma caused by disruption of the internal elastic lamina could be depicted as surface dilatation of dissecting arteries.17 BPAS-MRI illustrates the outer contour of the vertebrobasilar artery, free from the influence of flow or thrombus, whereas other established imaging modalities, such as MRA or DSA, show the inner contour of the vessels.5 Furthermore, the procedure of BPAS-MRI is very simple, requiring about 1 minute, and available with most MRI machines. In patients who have a dilated surface appearance of the VA and aneurysmal dilatation, stenosis, or occlusion, additional imaging, such as multisectional CTA, SPGR–MRI, and DSA, should be considered to confirm the diagnosis of VA dissection. When the optimal cutoff is applied, the sensitivity and specificity of BPAS-MRI may not be sufficiently high. The low sensitivity might be because of inappropriate timing of BPAS-MRI. In pseudonegative case, the timing of BPAS-MRI might be too late for evaluation of appropriate surface dilatation of the VA. Images without a dilated VA surface could be caused by regression of the surface dilatation in acute VA dissection. Repeated imaging might improve the sensitivity of this method. The low specificity can be explained by dilatation of the vessel not because of dissection but vascular remodeling caused by atherosclerotic change. Of the 4 pseudopositive patients, 3 showed complete occlusion of the VA on TOF-MRA. If additional imaging could not reveal a double lumen or intimal flap, such cases would be diagnosed as largeartery atherosclerosis. However, because the present study is based primarily on neuroradiological factors, there is no denying the possibility that the criteriabased diagnosis overlooked true dissection. Although
R. ITABASHI ET AL.
6
there were no patients with extracranial VA dissection in the present LMI series, BPAS-MRI is useless for evaluating the extracranial VA, which is another drawback of BPAS-MRI. In any event, because of its simplicity and safety, we believe that BPAS-MRI is a useful tool for the diagnosis of spontaneous VA dissection in patients with acute LMI.
References 1. Minematsu K, Matsuoka H, Kasuya J. Cervicocephalic arterial dissection in Japan: analysis of 454 patients in the spontaneous cervicocephalic arterial dissection study I (SCADS-I) (abstract). Stroke 2008;39:566. 2. Caplan LR. Dissections of brain-supplying arteries. Nat Clin Pract Neurol 2008;4:34-42. 3. Kim JS. Pure lateral medullary infarction: clinicalradiological correlation of 130 acute, consecutive patients. Brain 2003;126:1864-1872. 4. Hosoya T, Watanabe N, Yamaguchi K, et al. Intracranial vertebral artery dissection in Wallenberg syndrome. AJNR Am J Neuroradiol 1994;15:1161-1165. 5. Nagahata M, Abe Y, Ono S, et al. Surface appearance of the vertebrobasilar artery revealed on basiparallel anatomic scanning (BPAS)-MR imaging: its role for brain MR examination. AJNR Am J Neuroradiol 2005; 26:2508-2513. 6. Hamaguchi T, Yamada M. Basiparallel anatomic scanning-magnetic resonance imaging in vertebral artery dissection. Arch Neurol 2009;66:276-277. 7. Takemoto K, Takano K, Abe H, et al. The new MRI modalities ‘‘BPAS and VISTA’’ for the diagnosis of VA dissection. Acta Neurochir Suppl 2011;112:59-65.
8. Samuels OB, Joseph GJ, Lynn MJ, et al. A standardized method for measuring intracranial arterial stenosis. AJNR Am J Neuroradiol 2000;21:643-646. 9. Sato S, Toyoda K, Matsuoka H, et al. Isolated anterior cerebral artery territory infarction: dissection as an etiological mechanism. Cerebrovasc Dis 2010;29:170-177. 10. Adams HP Jr, Bendixen BH, Kappelle LJ, et al. Classification of subtype of acute ischemic stroke: definitions for use in a multicenter clinical trial. TOAST: Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993;24: 35-41. 11. Pelkonen O, Tikkakoski T, Pyhtinen J, et al. Cerebral CT and MRI findings in cervicocephalic artery dissection. Acta Radiol 2004;45:259-265. 12. Yamada SM, Nakane M, Aoki M, et al. Dissecting aneurysm of the anterior cerebral artery with severe subarachnoid hemorrhage during treatment for cerebral infarction. Int Med 2003;42:433-435. 13. Mokri B, Houser OW, Sandok BA, et al. Spontaneous dissections of the vertebral arteries. Neurology 1988; 38:880-885. 14. Levy C, Laissy JP, Raveau V, et al. Carotid and vertebral artery dissections: three-dimensional time-of-flight MR angiography and MR imaging versus conventional angiography. Radiology 1994;190:97-103. 15. Mascalchi M, Bianchi MC, Mangiafico S, et al. MRI and MR angiography of vertebral artery dissection. Neuroradiology 1997;39:329-340. 16. Chen CJ, Tseng YC, Lee TH, et al. Multisection CT angiography compared with catheter angiography in diagnosing vertebral dissection. AJNR Am J Neuroradiol 2004; 25:769-774. 17. Mizutani T, Kojima H, Asamoto S, et al. Pathological mechanism and three-dimensional structure of cerebral dissecting aneurysms. J Neurosurg 2001;94:712-717.