Introduction

   Those with asymptomatic high grade carotid stenosis (>70% according to North American Symptomatic Carotid Endarterectomy Trial[NASCET] criteria) had a 2 to 5% incidence of hemodynamic ischemic stroke or thromboembolic stroke a year.¹⁹⁾ It is not clear yet how long severe carotid stenosis usually takes to develop and become an occlusion and what factors contribute to increasing the severity of carotid stenosis. In addition, hemodynamic insufficiency or thromboembolic infarction can occur anytime in patients with asymptomatic high grade carotid stenosis, making a conservative medical approach less liable. Several case reports reported that the carotid endarterectomy(CEA) was more effective than medical therapy to reduce risks of ischemic strokes in symptomatic or asymptomatic patients with high grade carotid stenosis. Thus CEA was considered the treatment of choice for carotid senosis.²²⁾ The CEA involves the removal of thromboembolic source of the stenotic plaque built up on the artery wall and the reestablishment of cerebral blood flow.^15)16)17) During the past decade, many endovascular surgeons came to embrace PTA as a primary surgical treatment for severe carotid stenosis and recommend PTA as an alternative to CEA, citing its clinical effectiveness, convenience and safety.^7)13)14) There was a case in which severe carotid artery stenosis developed into acute carotid occlusion, so an emergent intra-arterial thrombolysis was performed in an attempt to recanalize total occlusion. And then PTAS was performed to prevent a residual high grade stenosis from becoming occluded, leading to a successful outcome.⁶⁾ In case the location of carotid stenosis makes the performance of CEA or PTAS difficult, an EC-IC bypass surgery can be a more effective surgical approach in consideration of collateral flow and neurological status.¹²⁾
   The aim of the study was to suggest an appropriate management for patients with carotid occlusive disease by analyzing treatment approaches and assessing, postoperative complications and prognosis in patients treated by authors.

Patients and Methods

1. Patient population
   A total of 52 patients(39 men and 13 women, mean age of 59 years, range 33-78 years), who presented with high grade carotid stenosis(37) or carotid artery occlusion(16) between Apr 1999 and Dec 2003, were investigated, retrospectively. Among them, 9 patients were treated with PTA alone, 28 patients with PTAS, 9 patients with EC-IC bypass surgery, 3 patients with PTAS followed by EC-IC bypass surgery and 3 patients with CEA.

2. Management

1) Carotid artery stenosis
   The brain parenchyma lesion, carotid artery stenosis, atherosclerosis and cerebral blood flow were measured using MRA, Carotid ultrasonography and SPECT. The presence of stenosis was confirmed at four vessels digital subtraction angiography(DSA). Patients with high grade stenosis in exclusion criteria of CEA were performed by PTA and/or PTAS. EC-IC bypass surgery was performed lately for the patients with long segment of ICA stenosis or tandem severe stenosis appearing the decreased reserve capacity of middle cerebral artery territories on ipsilateral hemisphere by SPECT. Carotid endarterectomy(CEA) was performed for the patients with over 90% stenosis and ulceration of proximal portion of the internal carotid artery. Bilateral decompressive craniectomy was done for the patient with massive brain edema following any treatment.

2) Carotid artery occlusion
   Among below 75 year old patients, those who met the inclusion criteria for thrombolysis(Table 1) were diagnosed using perfusion CT first. Those whose CT scanning showed decreased CBF and/or delayed TTP in carotid artery lesion side hemispheric subsequently underwent DSA to make sure the presence of high grade carotid artery stenosis or occlusion. DSA revealed complete occlusion at the intracranial or extracranial portion of the ICA with no development of collateral flow through the anterior communicating artery, posterior communicating artery or external carotid arteries. Patients with carotid artery occlusion were treated with intra-arterial thrombolysis and/or subsequent PTAS for the residual stenosis at the intracranial or extracranial origin site of internal carotid artery(ICA).

3) Clinical evaluation according to managements
   The variables, including the cause of stenosis or occlusion, preoperative clinical condition(NIHSS), the degree of stenosis, collateral blood supply in cerebral angiogram, age and gender, were analyzed to examine the appropriateness of different surgical procedures. At the same time, related complications, Barthel Index(BI), Glasgow outcome scale(GOS) and restenosis were examined to assess clinical outcomes of surgical procedures. To that end, the study was intended to suggest the best possible therapeutic strategy for patients with carotid occlusive disease.

Results

   The causes of high grade carotid stenosis or occlusion in 52 patients were classified four categories：40 atherosclerosis, 9 dissections, 2 traumas and 1 FMD. Different surgical procedures were undertaken depending on causes of stenosis： PTA alone was performed in 9 patients, PTAS for 28 patients, PTAS followed by EC-IC bypass surgery for 3 patients, EC-IC bypass surgery for 9 patients and CEA for 3 patients (Table 2). Preoperative clinical conditions according to NIHSS included atherosclerosis 4.9(range 1-19), dissection 7.8(2-13), FMD 2 and trauma 5.5(0-11)(Table 3). The surgical approaches based on the location of stenosis were as varied as PTAS performed for 24 out of 36 cases in which stenosis was found in the lower cervical ICA and PTA and PTAS performed for 3 and 4 cases, respectively, in which stenosis was detected in the upper cervical ICA(Table 4). The management approaches also varied with initial NIHSS：PTA was performed for 8.2(range 2-13), PTAS for 5.3(1-19), EC-IC bypass surgery for 3.7(2-6) and CEA for 1.3(1-2)(Table 5). Clinical outcomes of each procedure were evaluated between 3 and 12 months after surgery. The BI and GOS were average BI 64.4/GOS Excellent 3, Good, 4, Fair 1, Poor 1 in patients who underwent PTA, average BI 66.6/ GOS Excellent 10, Good, 9, Fair 4, Poor 3, Dead 2 in PTAS group, average BI 41.7/ GOS Good 1, Fair 2 in the group for which PTAS followed by EC-IC bypass surgery, average BI 86.7/ GOS Excellent 9 for the EC-IC bypass group and average BI 91.7/ GOS Excellent 3 for the CEA group(Table 5). The mean degree of stenosis was reduced from the preoperative degree of 80% to 33.8% after surgery in the PTA group, from 85.8% to 9.8% in the PTAS group, from 84.9% to 51.3% in the group in which PTAS followed by EC-IC bypass surgery and from 94% to 3.3% in the CEA group. The preoperative stenosis of 95.6% became 100% total occlusion after surgery in the EC-IC bypass group(Table 6). An EC-IC bypass surgery was performed in 3 restenosis cases during the follow-up examination period. Complications related with PTA and PTAS were 3 intracerebral hemorrhage, 1 intraventricular hemorrhage, 4 hyperperfuion syndrome, 2 thromboemobolic infarction, 4 severe brain edema.

Representative Cases

1. Case 1：Local thrombolysis followed by PTA
   A 63 year-old male patient was admitted to the hospital three hours after a sudden right hemiparesis. He had had several transient ischemic attacks(TIA) during the last five years. His NIHSS was 5 at admission. The angiography showed a total occlusion, caused by arterial dissection, of the left proximal portion of the ICA and the availability of the collateral circulation(Fig. 1A, B). A 300000 IU of urokinase was administered intraarterially immediately, and then ICA total occlusion was partially recannalized(Fig. 1C). PTA was performed immediately in the portion of the artery with severe residual stenosis, which was dilated to 33.3% of the stenotic diameter(Fig. 1D). Symptoms continued to improve after PTA, and the patient was discharged 3 weeks later without neurological deficit.

2. Case 2：PTAS
   This 65-year-old man was hospitalized with 3 times of transient hemiparesis during last 2 month. Angiography revealed severe stenosis of 10 cm above the origin of the left ICA(Fig. 2A). Angioplasty followed by stenting was successfully performed, and the repeated angiography was shown no residual stenosis or thrombus(Fig. 2B). Neurological examination 6 month later revealed no motor weakness any more.

3. Case 3：STA-MCA anastomosis
   A 54 year-old man presented with sudden dysarthria and left hemiparesis, the symptoms developed three days before. Angiography revealed the occlusion of the proximal portion of both ICA and that the presence of collateral flow via the posterior circulation in the left ICA territory(Fig. 3A, B). A single-photon emission computerized tomography(SPECT) showed severe hemodynamic insufficiency in the right ICA territory(Fig. 3C). A right STM-MCA anastomosis was performed at the 7th week after the onset of neurological impairment. The post-operative SPECT scans showed a complete disappearance of steal phenomenon(Fig. 3D). His symptoms improved enough to let him regain a normal life.

4. Case 4：CEA
   A 65-year old woman was admitted with transient hemiparesis which repeated several times during the last three months. Angiography revealed severe stenosis(90%) of the proximal portion of right ICA(Fig. 4A). CEA was performed while the patient was awakened. The postoperative computed tomogram angiography(CTA) confirmed that the narrowed blood vessel opened up to nearly normal size(Fig. 4B).

Discussion

   Given high rates of mortality and morbidity in patients with high grade carotid stenosis or carotid occlusion, it is commonly agreed among specialists that more aggressive approaches are required for the treatment of strokes. Carotid endarterectomy(CEA) was the most common surgical procedure for patients with symptomatic or asymptomatic high grade stenosis of extracranial portion of ICA.¹⁰⁾ CEA, however, had methodological limitation to be deemed a standard procedure because CEA alone can not be done in multiple contexts, including patients with high cervical carotid stenosis, radiation induced stenosis, tandem lesion, carotid stenosis associated with contralateral occlusion or vertebrobasilar artery stenosis or other medical problems.¹⁾²⁾ The advent of endovascular procedure enables stroke specialists to perform PTA or PTAS for the treatment of both extracranial and intracranial ICA stenosis and even vertebrobasilar artery stenosis. And the two procedures are considered alternative surgical access from CEA.⁹⁾¹⁰⁾ However, there is no consensus regarding indications for angioplasty and stenting. This study aimed at discussing strategy for surgical management of 52 patients with ICA high grade stenosis or occlusion by retrospectively analyzing surgical procedures that they underwent.

1. Stenosis pathogenesis, site, NIHSS and management
   ICA stenosis in patients was largely initiated by atheroscrelosis(76.9%). Among patients with atherosclerotic stenosis, 4 ended up having occlusion. All of 9 patients(17.3%) with dissection-induced stenosis, along with 2 other patients with trauma-induced stenosis, also had total occlusion, bringing the total number of patients with total ICA occlusion to 15. Patients who presented with dissection-induced stenosis had a higher mean NIHSS score with 7.8 than those with ICA stenosis caused by any other disorders. The higher NIHSS score was likely due to the sudden blockage of blood vessel and poor collateral blood, which were resulted from an acute ICA occlusion. This finding supported that dissection-induced stenosis represents a more serious neurological impairment than other types of stenosis in which the supply of blood gradually decreases.
   Occlusion of the cervical internal carotid artery(ICA) without collateral flow is one of the most critical forms of acute ischemia. A review of literature by Meyer et al.¹⁸⁾ revealed that 16% to 55% of patients with acute ICA occlusion and profound neurological deficits will die of complications from infarction, 40-60% will be left with severe neurological disability, and only 2 % to 12% will make a good recovery. Therefore, the emergent management of acute symptomatic carotid artery occlusion should be done immediately and properly after the onset of the occlusion. All of 9 patients with dissection-induced occlusion underwent an emergent thrombolysis and subsequent PTA or PTAS after they were admitted to the emergency room. Among these 9 patients, 4 had an excellent outcome, defined by GOS score, while the other five patients had fair or poor outcomes. Of four patients with excellent outcome showed the preoperative NIHSS score of 3 or less and well-established collateral flow although their ICA stenosis became occluded. Cohen⁶⁾ and Vasquez et al.²³⁾ reported successful results of thrombolysis and stenting that were performed emergently for patients with carotid dissection as diffusion/ perfusion mismatch on MRI was observed. All of 6 patients with ICA occlusion caused by other disorders than dissection had the preoperative NIHSS score of 3 or less and the blood flow was maintained by collateral circulation according to cerebral angiography. But they developed hemodynamic insufficiency and showed significantly decreased reserve capacity according to SPECT scans. After ECIC bypass surgery, all of these six patients had an excellent outcome. It is therefore likely that the prognosis in patients with ICA occlusion mainly depends on the extent of collateral flow available in the ICA territory during the whole period until a surgery was performed for ICA occlusion.
   It is almost mandatory that CEA or PTAS is performed for patients with severe atherosclerotic stenosis, whether symptomatic or asymptomatic, if the stenosis is located in the lower cervical ICA.¹⁹⁾ Authors performed PTAS in 23 patients with severe atherosclerotic stenosis and PTA in 5 patients with the same severity of stenosis. Authors also performed PTAS in 4 patients with severe stenosis of high cervical region of ICA without any problems. Thus PTAS was usually performed in case the stenosis was located in the lower cervical region, and PTA was conducted in the beginning after carotid artery stenting in case with severe stenosis of intracranial portion of ICA if PTAS is not easy to be performed. The rapid development in stent applications has made the stenting of stenosis of the intracranial ICA possible.¹¹⁾

2. Management and outcome, related complications
   Among postoperative complications, 3 ICH and 1IVH appeared to be more closely related to intra-arterial thrombolysis than surgical procedures such as PTA and PTAS because the hemorrhage was too big to be considered as hemorrhagic infarction induced by thromboembolism.^8)18)24) But 4 hyperperfusion syndrome, 2 thromboembolism and 3 restenosis complications appeared to be associated with PTA and PTAS. Patients who had hyperperfusion syndrome and thromboembolic infarction after surgery successfully recovered without any sequelae. The recent advancement in the development of filter protection system has led to a considerable decline in complications of thromboembolism.^3)26)27) Three patients who developed late restenosis had had stenosis of 51.3% after surgery and underwent STA-MCA anastomosis as it is the only choice for severe stenosis. After the direct bypass surgery, the mean BI score was 41.7, showing a poor outcome. Even those patients who had higher NIHSS scores showed a poor outcome, regardless of the type of surgery. Four patients who had brain edema after surgery underwent various medical and surgical therapies such as decompressive craniectomy under the assumption that their brain edema probably occurred as a result of ICH, reperfusion injury or ischemic brain edema. But two of them died and the other two fell into a coma vigil.

3. Management option
   Although the type of surgical procedure did not have a direct impact on clinical outcome in patients with high grade carotid artery stenosis or occlusion after surgery, the preoperative condition of cerebral collateral circulation was a significant factor affecting the outcome in these patients. The selection of management procedure was particularly vital for patients with tandem carotid stenosis, bilateral carotid stenosis, carotid occlusion with contralateral carotid stenosis, and carotid stenosis with vertebrobasilar artery stenosis.^{4)5)20)21)25)} Since these high risk patients are more prone to develop a neurological sequelae after a temporary blockage of blood flow that could happen accidentally during surgery. It is important to choose a proper management after considering the cerebral collateral circulation, symptomatic or asymptomatic patients, preoperative clinical condition, age and the location and degree of stenosis or occlusion.⁴⁾

Conclusion

   The authors of the study drew conclusions about the management strategy for patients with carotid occlusive disease. The authors strongly recommend the use of PTAS for patients who have had symptomatic or asymptomatic high grade (70-99%) carotid stenosis with good collateral flow and those who are high surgical risk patients, but the use of CEA would be more effective for patients who are asymptomatic high grade stenosis patients and high intervention risk patients. Both emergent thrombolysis treatment and PTA and/or PTAS should be undertaken for patients with acute carotid occlusion who meet the inclusion criteria presented. An EC-IC bypass surgery would prove effective in the treatment of patients with chronic carotid occlusion(long segment stenosis, tandem stenosis, restenosis of not easily to be performed PTAS again) who developed hemodynamic insufficiency, which in turn results in any neurologic defects.

REFERENCES

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6. Coh