A case of intimal hyperplasia induced by stenting for vertebral artery origin stenosis: Assessed on intravascular ultrasound Kentaro Hayashi, Naoki Kitagawa, Minoru Morikawa* and Makio Kaminogo Department of Neurosurgery, *Department of Radiology, Nagasaki University School of Medicine, Nagasaki, Japan We report a case of proximal vertebral artery restenosis following stent placement. Intravascular ultrasound study helped delineate its characteristics. A 69-year-old man was admitted because of dysarthria and dysphagia. Angiography revealed hypoplasia of left vertebral artery (VA) and remarkable stenosis of the proximal right VA with inadequate collateral ow from the anterior circulation. Balloon angioplasty and stent placement at the VA was performed to an excellent angiographic result with recovery of neurological symptoms. His condition deteriorated six months later due to intimal hyperplasia, which we evaluated by intravascular ultrasound (IVUS). Balloon angioplasty was then performed. Stent placement may induce intimal hyperplasia and IVUS is useful to assess the lesion. [Neurol Res 2003; 25: 357–360] Keywords: Vertebral artery stenosis; stent placement; intimal hyperplasia; intravascular ultrasound INTRODUCTION Percutaneous transluminal angioplasty (PTA) is thought to be a safe and effective procedure for the treatment of stenotic arterial lesions. Some atherosclerotic lesions have a poor response to angioplasty due to elastic recoil or early restenosis. Intraluminal stents are now widely used in the peripheral vascular system, cardiovascular system, and in the renal arteries to provide a supporting frame to keep the lumen patent and smooth walled. Stent exibility allows for easy maneuver through curves and tortuous vessels, such as a vertebral artery (VA)1 . However, restenosis occasionally occurs in stent placement cases2 . Direct intravascular (IVUS) assessment may be a useful technique for detection of plaques, to determine the size of lesion and appropriate stent size during the procedure3 . Additionally, an auxiliary technique for ow visualization using IVUS has been recently introduced4 . We present a case whereby ultrasound imaging and ow imaging were utilized to identify proximal VA restenosis following stent placement. This situation illustrates the utility of IVUS and emphasizes the important role that IVUS plays in this delicate intervention. CASE REPORT A 69-year-old man was initially admitted to another hospital following repeated episodes of oating sensation, dysarthria and dysphasia. He gave a history of angina pectoris, hypertension, diabetes mellitus and hyperlipidemia. These symptoms were improved after Correspondence and reprint requests to: Kentaro Hayashi, MD, Department of Neurosurgery, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki-city, Nagasaki 852-8501, Japan. [Kentaro.Hayashi@ma8.seikyou.ne.jp] Accepted for publication February 2003. # 2003 Forefront Publishing Group 0161–6412/03/040357–04 plasma expanders and antiplatelet medication. Angiography revealed proximal right VA severe stenosis and hypoplastic left VA (Figure 1A). Collateral ow from anterior circulation was poor. The diagnosis of the vertebrobasilar insufŽciency was reached and elective endovascular recanalization was planned. After the administration of local anesthesia, 8-French sheath was introduced into the femoral artery. 8F guiding catheter was then navigated into the right subclavian artery and Avanar F/X imaging catheter (Jomed Inc., Rancho Cordova, CA, USA) was inserted to the right VA. Stenotic lumen was visualized with color ow imaging on In-Vision monitor (Jomed Inc.) (Figure 1B). Dilatation by 3-mm by 20-mm balloon catheter was performed. There was brief disturbance to consciousness during balloon ination. A 4-mm by 10-mm Palmaz stent (Johnson & Johnson, Arlington, TX, USA) mounted on a 5-mm by 20-mm angioplasty balloon was then placed at the ostial origin. An angiogram following the stent placement revealed widely patent proximal VA with stent in place (Figure 1C ). Immediately after stent placement, IVUS was performed to assess the treated vessel (Figure 1D). Mild arterial dissection occurred after balloon angioplasty, that was corrected by stent placement. No major peri-operative complication occurred apart from a mild transient consciousness disturbance. His symptoms improved signiŽcantly and he was maintained on warfarin and aspirin therapy. Approximately six months after stent placement, his symptom frequency and severity began to increase. Angiography revealed subocclusive restenosis on proximal portion of the stent placement (Figure 2A). Imaging catheter focusing at the restenosis revealed homogenous lesion inside the stent, indicating an intimal hyperplasia (Figure 2B). Dilatation was perforfmed by 3-mm by 20-mm angioplasty balloon catheter under local anesthesia. This Neurological Research, 2003, Volume 25, June 357 Stent induced intimal hyperplasia assessed on IVUS: Kentaro Hayashi et al. Figure 1 A: Right subclavian artery angiogram showing severe stenosis of VA origin. B: Cross-sectional IVUS image of the VA oriŽce. Color ow help identify stenotic lumen. The ow of subclavian artery is widely identiŽed from 6 to 9 o’clock. C: Right subclavian artery angiogram immediately post-angioplasty demonstrating complete reversal of stenosis. D: IVUS with color ow after original deployment. Color ow areas help identify widely opened vascular lumen resulted in a residual 10% to 20% stenosis of the origin of the right VA with acceptable blood ow (Figure 2C,D). There was no serious complication caused by the PTA procedure. Post-operative course was uneventful and he is doing well more than one year after the second recanalization procedure. DISCUSSION Restenosis is a major long-term success limiting factor after PTA procedure. The recent development of stenting has led to an evident improvement of PTA results, reducing restenosis and effecting a low morbidity and mortality5 . Lesions of VA origin tend to restenose. Restenosis presents in a number of ways, such as from atherosclerosis, elastic recoil, stent deformity and intimal hyperplasia6 . Atherosclerotic restenosis usually takes an indolent course7 . Generally it takes more than one year 358 Neurological Research, 2003, Volume 25, June following the procedure. In this patient restenosis took six months to occur. Although, in this VA portion, elastic recoil is seen frequently after PTA, it is usually rare after stenting. In peripheral arteries such as carotid artery, the mechanical stress induces stent deformity. Mechanical stress from the outside seems to be unlikely since VA origin is anatomically located deep under the clavicle. Sometimes, subclavian artery or nerve get compressed by anterior scalenus muscle and middle scalenus muscle inducing thoracic outlet syndrome. The best possible cause for stent restenosis in this case is considered to be intimal hyperplasia6,7 . Pathophysiology of this thickening is thouight to be a remodeling failure of the arterial wall along with excessive and disorderly proliferation of smooth muscle cells8 . Local inammation is thought to be important in the pathogenesis. Excessive arterial wall injury or stimulation during intervention may induce local inammation. In this case, small arterial dissection Stent induced intimal hyperplasia assessed on IVUS: Kentaro Hayashi et al. Figure 2 A: Right subclavian artery angiogram obtained six months post-stenting showing severe restenosis of right VA origin. B: Cross-sectional IVUS image of the restenotic lesion. Blood ow was not seen despite color image, because the probe was wedged to the stenotic lumen. Homogeneous lesion was detected inside the stent struts, indicating intimal hyperplagia (arrow). C: Right subclavian artery angiogram after second PTA. Balloon dilatation with angioplasty catheter resulted in a residual 10% to 20% stenosis of the origin of the right VA. D: IVUS with color ow after second PTA. Acceptable blood ow was detected during angioplasty, which was corrected by stenting, may be associated with neointimal formation. Some animal experiments have highlighted the possibility of inhibiting the migration of smooth muscle cell by either conventional medication, gene delivery or irridiation9 . Clinical trials are currently in progress1 0 . IVUS imaging provides real-time information in the interventional setting, affording a unique perspective on which to base decisions such as adequacy of balloon deployment, cross sectional percent stenosis and residual stenosis, and the creation of aps and dissections. The operator is thus given more comprehensive data that can direct further treatment, such as redilation or stent placement. For these reasons, IVUS is being used more frequently in the treatment and assessment of endovas- cular lesions4 . In this patient, restenosis appeared after six months from the stent placement, suggesting that the cause of restenosis is intimal hyperplasia. Furthermore, IVUS demonstrated the lesion inside the stent struts without stent deformity. The IVUS show us real-time, 360 degrees view of vascular lumen during the endovascular procedure. Additionally, a newly introduced color ow imaging technique can allow easy identiŽcation of the region of blood ow. More exible monorail type probe catheters are available that make it more easy to evaluate lesions in the tortuous vessels. At present, most stents are poorly deŽned angiographically since they are invariably radiolucent. Thus IVUS proves its usefulness in this respect. However, the cost effectiveness is still under investigation. Therefore, the Neurological Research, 2003, Volume 25, June 359 Stent induced intimal hyperplasia assessed on IVUS: Kentaro Hayashi et al. use of IVUS is currently established at special research centers. There are some strategies for restenosis such as surgical reconstruction or repeated PTA. Sometimes these lesions are surgically inaccessible and pose a greater potential risk. One such technique includes transection of the vessel above the stenosis, then re-implanting it either at the ipsilateral carotid artery or subclavian artery1 1 . As such, additional risks of injury to the sympathetic Žbers, the phrenic, recurrent laryngeal, vagus or thoracic nerves, as well as the potential for pulmonary complications from the thoracotomy are possible12 . To minimize this, Ogawa et al.13 introduced relatively less invasive surgical reconstruction without thoracotomy or artiŽcial heart-lung machine. By and large, PTA is now a well established therapeutic alternative to operative reconstruction of proximal VA stenosis and seems to be relatively safe. No mortality has been reported after PTA. Higashida et al.14 report of 34 patients who underwent angioplasty for proximal VA, where the restenosis rate was 8.8%. Restenosis cases were successfully treated by repeated balloon angioplasty. PTA is minimally invasive and it was chosen for this case. Although the patient is doing well more than one year from second procedure, the possibility of restenosis can not be deŽnitely ruled out. Prolonged follow-up is therefore needed. CONCLUSION Stent placement may induce intimal hyperplasia and IVUS is useful to assess the lesion. REFERENCES 1 Malek AM, Gigashida RT, Phatouros CC, Lempert TE, Meyers PM, Gress DR, Dowd CF, Halbach VV. Treatment of posterior circulation ischemia with extracranial percutaneous balloon angioplasty and stent placement. Stroke 1999; 30: 2073–2085 360 Neurological Research, 2003, Volume 25, June 2 Chastain HD, Campbell MS, Iyer S, Rousin GS, Witek J, Mathur A, Al-Mubarak NA, Terry JB, Yates V, Kretzer K, Alred D, Gomez CR. Extracranial vertebral artery stent placement: In-hospital and follow-up results. J Neurosurg 1999; 91: 547–552 3 Nissen SE, Yock P. Intravascular ultrasound novel pathophysiological insight and current clinical applications. 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