Stroke in patients with occlusion of the internal carotid artery: options for treatment.

Expert Review of Neurotherapeutics Downloaded from informahealthcare.com by UMEA University Library on 09/07/14 For personal use only.

Review

Stroke in patients with occlusion of the internal carotid artery: options for treatment Expert Rev. Neurother. Early online, 1–15 (2014)

John Ih Lee, Sebastian Jander, Alexander Oberhuber, Hubert Schelzig, Daniel Ha¨nggi, Bernd Turowski and Ru¨diger J Seitz* LVR-Klinikum Du¨sseldorf, University Hospital Du¨sseldorf, Du¨sseldorf, Germany *Author for correspondence: [email protected]

Ischemic stroke may occur in patients in whom vascular imaging shows the ipsilateral internal carotid artery (ICA) to be occluded. In younger patients this is often due to carotid artery dissection, while in older people this most likely results from cardiac embolism or thrombosis secondary to high-grade stenosis at the carotid bifurcation. Interventional techniques aim at recanalization of the carotid artery for early restoration of cerebral blood flow and secondary prevention of future strokes. In chronic ICA occlusion the ischemic infarct may be related to hemodynamic compromise. In this situation, extracranial-intracranial bypass surgery was introduced, but its role remains still unclear. Ischemic stroke may also occur in patients with a chronic occlusion of the contralateral ICA. This situation demands the usual stroke treatment, but surgical and neuroradiological interventions face a higher risk than unilateral vascular pathology. Medical treatment supports stroke prevention in carotid artery occlusion. KEYWORDS: carotid artery occlusion • carotid surgery • interventional recanalization • ischemic stroke • stroke prevention • vascular imaging

Ischemic stroke is caused by a sudden occlusion of a cerebral artery resulting in a downstream brain infarct. The causes are different but have been proposed to be useful for stroke subtyping based on diagnostic evidence [1]. Ischemic brain infarcts can be due to small artery disease leading to small lacunar-type subcortical infarcts. They typically go ahead with functionally relevant neurological deficits due to damage of corticofugal motor, spinocortical somatosensory and/or cerebello-cortical fibers [2,3]. Thromboembolic occlusions of the main stem of the large cerebral arteries or of their branches lead to territorial brain infarcts, which affect parts of the cerebral cortex and the underlying hemispheric white matter [4]. Efficient collaterals and early recanalization of the occluded artery are able to counteract the manifestation of an ischemic brain infarct such that the volume of the manifest infarct turns out to be smaller than the entire perfusion territory of the affected artery. This is most apparent in thromboembolic infarcts of the middle cerebral artery (MCA) in which

informahealthcare.com

10.1586/14737175.2014.955477

efficient collaterals and early MCA recanalization typically lead to limitation of the infarct to the striatocapsular region [4]. Most likely the small lenticulostriate arteries that originate directly from the MCA stem remain occluded for a longer period of time leading to a most severely depressed cerebral perfusion and often secondary cerebral hemorrhage [5]. Ischemic stroke may occur, however, also in the presence of an occlusion of the internal carotid artery (ICA). The clinical situation is straight forward, if the infarct occurs in the cerebral hemisphere opposite to the side of the ICA occlusion. In this case, the ICA occlusion is chronic and pre-existing relative to the acute stroke event. In this situation, the acute stroke is either of cardioembolic origin, of lacunar small artery-type origin or of arterio-arterial emboli due to arteriosclerotic changes of the aortic arch [6] or a stenosis of the ipsilesional ICA. Consequently, treatment is determined by the current guidelines of how to treat acute stroke and how to introduce secondary preventive treatment. It should be mentioned, however,

Ó 2014 Informa UK Ltd

ISSN 1473-7175

1

Review


A

Lee, Jander, Oberhuber et al.

B

C

Diagnostic investigations of the extracranial & intracranial arteries

Acute stroke treatment and secondary stroke prevention require information in the individual patient about the localization of arterial stenoses and occlusions, the presence of collaterals and their implications for cerebral perfusion. Doppler sonography combined with Duplex sonography is the mainstay for non-invasive diagnosis of cerebral artery disease as described in detail by Byrnes and Ross [14]. Figure 1. Acute internal carotid artery occlusion in a patient with an acute hemiparetic stroke. (A + B) Multiple small emboligenic diffusion-weighted imaging The advantages of these methods are the lesions in cortical and white matter locations. (C) Time-of-flight magnetic resonance virtually ubiquitous availability and the angiography showing an absence of the ipsilesional internal carotid artery. Note the faint online demonstration of the local hemodysignal in the corresponding middle cerebral artery and the posterior communicating namics in the artery investigated. Their artery. No signal in the anterior cerebral artery. disadvantages, however, are the high methodological skill of the investigator, their that interventional or surgical revascularization procedures on high time demand and the indirect assessment of the degree of the side of the acute ischemic stroke face a higher risk of an artery stenosis by the hemodynamics. In fact, a number of periprocedural complications than without a contralateral ICA functional and structural parameters need to be assessed to deterocclusion [7]. mine the degree of a stenosis [15]. Concerning an occlusion of the More complicated is the situation, when a transient ischemia ICA, the situation becomes even more complicated, since the or an acute stroke occurs on the side of the ICA artery does not show a flow signal in Duplex sonography but a occlusion (FIGURE 1). Then, it needs to be determined, if the ische- severely abnormal monophasic or bidirectional signal in Doppler mic event are the clinical manifestation of an acute ICA occlu- sonography. Due to the limited spatial resolution, however, it sion or if the ICA occlusion was chronic and, thus, pre-existing. cannot be excluded that a small residual vessel lumen with a maxIn fact, we are confronted with two different situations that imally slowed blood flow is still present [16]. Therefore, radiologihave a completely different pathophysiology and, thus, demand cal methods for structural visualization of the artery may become completely different therapeutic actions. In both situations, mandatory in such situations. however, the contralateral ICA as well as the vertebral arteries is Three radiological methods for vascular imaging can be used of high relevance. Multimodal stroke imaging with computed to demonstrate pathology of the extracranial and intracranial tomography (CT) or magnetic resonance imaging (MRI) pro- arteries. Catheter-angiography with the digital subtraction angivide the mandatory information about the extent of ischemic ography (DSA) technique is the gold standard for the diagnosis brain damage and the degree of impaired brain perfusion such of ICA occlusion (FIGURE 2). It allows the assessment of the vascuthat therapeutic decisions can be made promptly. Accordingly, lar lumen with the highest accuracy due to intra-arterial (IA) multimodal stroke imaging can inform about the cause of the administration of the contrast medium. However, catheteracute neurological deficit and the potential prognosis [8–10]. In a DSA is an invasive method implying a certain risk of vascular chronic ICA occlusion, the hemodynamic deprivation may be and neurological complications such as local hemorrhage and severe due to arteriosclerotic disease in multiple cerebral arteries vessel dissection at the puncture site as well as catheter-related or a virtually normal cerebral perfusion may result from a thromboembolism with subsequent stroke. These risks increase recruitment of cerebral collaterals [11,12]. Thus, CT and MRI with increasing age of the patients and the prevalence of occluangiographic investigations of the intracranial and extracranial sive artery disease [17]. Therefore, DSA is usually reserved for arteries are needed to demonstrate the location and the type of patients in whom clinical evidence indicates a high probability artery occlusions. An extracranial ICA occlusion can occur in an of IA intervention. In most other cases, non-invasive imaging arteriosclerotic high-grade stenosis of the ICA as typically in the approaches are therefore preferred. elderly. An intracranial ICA occlusion may result from an emboNon-invasive angiographic methods are computed tomogralism into the distal part of the ICA with a secondary occlusion phy angiography (CTA) and magnetic resonance angiography of the MCA [13]. In younger people, ICA occlusion can result (MRA). CTA requires the intravenous application of contrast from a dissection of the ICA bare of arteriosclerosis. This differ- medium, while MRA can be performed without additional entiation is crucial since the therapeutic implications are differ- contrast-application with the so-called time-of-flight (TOF) ent in these situations. technique [18]. The spatial resolution of CTA is better than in In fact, acute stroke treatment is an interdisciplinary MRA but worse than in DSA. In addition, in the vicinity of endeavor involving medical, interventional neuroradiological the skull-base there are severe artifacts in CTA. CTA like MRA and surgical procedures as will be discussed in this paper. gives a snap-shot of vessel structure but it does not deliver any doi: 10.1586/14737175.2014.955477

Expert Rev. Neurother.


Stroke in patients with occlusion of the ICA

Review

dynamic information (FIGURE 2). In the D E C A TOF technique of MRA the signal loss (flow void) due to the movement of blood particles between energy absorption (resonance) and energy emission within the frame of MR-excitation is used for imaging of the blood vessels. Thus, TOF imaging is brought about by the dynamics of blood flow and not by anatomic F B structures as in contrast-based imaging techniques. Due to this technical aspect, TOF-MRA is hypersensitive in depicting arterial stenoses and tends to overestimate them. Thus, the application of multiple non-invasive angiographic methods was recommended to establish the diagnosis of an ICA occlusion [19]. Furthermore, CT as well as MRI gives information Figure 2. Stroke in a patient with occlusion of the internal carotid artery. about brain parenchyma and extracranial (A) Computed tomography (CT)-perfusion reveals an area of hemodymic compromise perivascular structures. Owing to a higher corresponding to the acute hemiplegia. (B) CT-angiography shows the occlusion of the corresponding internal carotid artery. (C) Digital subtraction angiography shows a typical sensitivity, MRA provides more informapresentation of an internal carotid artery dissection. (D) Recanalization after stent tion about the content of the ICA lumen, implantation and intracranial thrombectomy. CT before (E) and after (F) successful that is, liquid blood with stasis, thromrecanalization showing only a small area of infarction. bosed blood or organized thrombus, and about the vessel wall than CTA. Source images of CTA or MRA together with Fluid Attenuated Inver- predict besides infarct manifestation also parenchymal hemorsion Recovery and T2-weighted MRI may show an intramural rhage, particularly after systemic thrombolysis as found in an hematoma suspicious of an arterial dissection. However, MRA pooled analysis of EPITHET and DEFUSE trial patients [24]. and CTA may overestimate the presence of an ICA occlusion Acute intracranial ICA occlusion due to false-positive findings [20]. An acute occlusion of the intracranial ICA may result from a thromboembolic occlusion by a large cardiac embolus. Patients Diagnostic investigations of cerebral tissue viability Assessment of perfusion of the brain parenchyma is of critical with atrial fibrillation and history of systemic embolism, female importance for demonstrating the spatial extent and severity of gender and advanced age are particularly prone to embolic ICA cerebral ischemia and the potential prognosis of stroke [21,22]. occlusion [25]. Typically, this leads to a distal intracranial occluTypically, perfusion imaging is based on dynamic recordings of sion of the ICA and is often accompanied by an additional CT or MRI aiming at assessing the passage of contrast medium occlusion of the MCA. Such patients present with a severe through the brain tissue (FIGURE 2). The signal intensity changes stroke syndrome and have particularly poor prognosis since the over time reflect the local dynamics of perfusion and can be blood supply is most severely compromised throughout the shown in a pixel-by-pixel manner in functional image maps. entire MCA territory and the anterior cerebral artery. In case These functional image maps show different variables of the of a direct origin of the posterior cerebral artery out of the cerebral hemodynamics [12,23]. These include simple assessments ICA the posterior cerebral artery may also be affected, which of the timing of contrast bolus in the brain in time-to-peak will additionally compromise the collateral flow in the affected (TTP) maps, modeled maps of timing of the passage of the hemisphere. Most often systemic thrombolysis may fail to procontrast bolus through the brain in so-called Tmax maps, and vide rapid and sufficient recanalization in a distal occlusion of maps of the mean transient time (MTT). Also, maps of cere- the ICA [26]. bral blood flow (CBF) and cerebral blood volume (CBV) can be computed. Although these methods are currently limited to Acute extracranial ICA occlusion specialized stroke centers, they allow detailed insight into stroke An acute occlusion of the extracranial ICA may be caused in pathophysiology in the given patient. The comparison with many instances by a local thrombotic occlusion in the presence maps of water diffusion in the brain tissue obtained with of a high-grade ICA stenosis, which is typically situated at the diffusion-weighted imaging (DWI) provides means for assessing ICA bifurcation. In high-grade arterial stenosis, the endothelial neurologically relevant but transient brain ischemia from severe cells are exposed to high shear effects and become prone to and irreversible ischemic brain damage as illustrated in FIGURE 3. mechanical injury. Such endothelial defects are prominent drivMoreover, a very low CBV in acute stroke was shown to ers of coagulation resulting in the local formation of thrombi, informahealthcare.com

doi: 10.1586/14737175.2014.955477

Review


45 TTP rCBV


Lesion volume (ml)

40 35

DWI

30

T2

25 20 15 10 5 0 Stable

At risk

Stroke

Figure 3. Multiparametric assessment of changes of cerebral perfusion and of the manifest brain lesions in stable chronic internal carotid artery occlusion, in chronic symptomatic internal carotid artery occlusion at risk of manifest ischemia, and in acute middle cerebral artery stroke. Note the absence of structural brain changes as assessed with DWI and T2-weighted MRI in stable asymptomatic chronic ICA occlusion despite the severe compromise of cerebral perfusion as evident from the large volume with a delayed TTP. In chronic symptomatic ICA occlusion, there are manifest DWI- and T2-lesions. In acute MCA stroke, there is severe ischemia with areas with a lack of perfusion as demonstrated by the rCBV. DWI: Diffusion-weighted imaging; ICA: Internal carotid artery; MCA: Middle cerebral artery; rCBV: Regional cerebral blood volume; TTP: Time to peak of the contrast bolus. Data taken from [11].

which may be transported downstream with the blood flow causing arterio-arterial infarct lesions [27]. In case of a massive initiation of a local thrombus formation, the ICA may become occluded locally by such a thrombus, which then may lead to a blood stasis in the entire ICA up to circuit of Willis and subsequent thrombus formation. Initially, the ICA occlusion is not complete and certainly not stable resulting in a carotid pseudoocclusion. This is a rare condition and characterized by a reduced antegrade flow into the ICA. Typical findings in DSA angiography are the antegrade string-like filling (string sign or slim sign) in the late phase or the retrograde filling up to the skull base [28]. Duplex sonography also provides important information in such a condition [29]. The patients may have amaurosis fugax or transient ischemic attack (TIA) or manifest stroke symptoms including hemiparesis or aphasia. These symptoms result from embolism into downstream cerebral arteries, for example, the MCA or small branches of the MCA, these smaller vessels may become all of a sudden obstructed (FIGURE 1). Typically, they affect both cortical and white matter regions. The thereby caused perfusion deficit typically induces an immediate onset of neurological symptoms. When small arterial vessels are affected, the symptoms may be transient and the structural brain lesions small even in DWI [11,12]. Such patients may respond to systemic doi: 10.1586/14737175.2014.955477

thrombolysis. Profoundly different is the situation when a large thrombus obstructs a proximal intracranial artery like the MCA stem. In such cases, the neurological deficit is that of a full-blown MCA infarct demanding rapid revascularization. Systemic thrombolysis may be much less effective than in arterial branch occlusion. In such cases, interventional neuroradiological procedures allowing to reopen the acutely occluded ICA and then to extract the embolus out of the MCA may be a therapeutic option with high efficacy in selected patients. Even interventional procedures with thrombus extraction via the contralateral carotid artery have been described as feasible and effective [30]. However, up to now broad evidence from randomized trials is virtually lacking [31]. Similarly, only a few retrospective studies exist about the surgical treatment of carotid pseudo-occlusion. The perioperative stroke rate ranges from 2.5 to 11.8%, with a mortality rate between 1.9 and 10%. Patency rates were 75.5–79% [32–34]. Most authors agree that after good patient selection, there is a benefit for carotid endarteriectomy (CEA) of a pseudo-occluded ICA. However, there is only a low incidence of this condition (largest series with 128 patients over a 13-year period [34]). Guidelines of the German vascular surgeons require consciousness of the patient, a patent MCA and a relatively small infarct lesion as criteria for an emergency carotid operation performed within 48 h after stroke onset [35]. Thrombolysis in thromboembolic ICA occlusion

As described in the previous section, brain infarcts caused by acute ICA occlusion are typically of thromboembolic origin and associated with extremely poor prognosis. Patients usually present with high National Institutes of Health Stroke Scale scores because of profound neurological deficits and have a high risk for persistent disability or death [36–39]. Acute ischemic stroke in acute ICA occlusion has a poor prognosis even when treated with systemic intravenous thrombolysis as found in a cohort study comparing 1700 patients without extracranial ICA occlusion to 137 with extracranial ICA occlusion [39]. Intravenous (IV) systemic thrombolysis with tissue plasminogen activator is currently approved as the first-line treatment for acute ischemic stroke [40,41]. Therefore, systemic thrombolysis has to be regarded as the first line of treatment also for symptomatic ICA occlusion presenting with acute ischemic stroke [41]. But recanalization rates were especially low after IV thrombolysis in acute ICA occlusion [42–44]. Importantly, there is no beneficial effect on patient outcome even after successful recanalization of an extracranial ICA occlusion with IV thrombolysis [45,46]. Rather, there is an increased rate of death and intracranial bleeding [47]. Interventional recanalization of thromboembolic ICA occlusion

A typical clinical finding is the combination of an extracranial and intracranial ICA occlusion. Either the intracranial thrombus might be caused by stasis or downstream embolus or a carotid-T-occlusion results in retrograde thrombosis of the Expert Rev. Neurother.



extracranial ICA. In these cases, interventional treatment with stenting of the extracranial occlusion followed by distal IA thrombectomy is the only treatment option (FIGURE 2). Stenting of the ICA is technically straightforward and adds only minutes to the procedure of intracranial thrombectomy. As long as a large intracranial artery is occluded by thrombotic material, the small peripheral arteries are protected from possible thromboembolic complications due to the stenting procedure. It was found to be successful leading to persistent revascularization when it was done within the first 48 h after occlusion [48]. It is of note that stent implantation requires platelet inhibition, which theoretically might increase the risk of reperfusion injury in already damaged brain tissue. In-house experience suggests that antiplatelet drugs in those circumstances did not result in a clinically relevant increase in hemorrhages. A recent meta-analysis of 32 studies and altogether 1107 patients showed that in the first 6 h stenting in extracranial ICA occlusion and mechanical thrombectomy in intracranial ICA and MCA occlusion were associated with higher recanalization rates and improved outcomes as compared with IA thrombolysis [48]. Similarly, in smaller studies revascularization of the cervical ICA occlusion prior to treatment of the intracranial occlusion led to increased rates of recanalization in patients with tandem extracranial and intracranial occlusions and was associated with greater survival rates [49,31]. In fact, intracranial thrombectomy with Solitaire stent was successful with a recanalization rate of 80% as found in a number of series of consecutive patients [30,50]. However, administration of recombinant tissue plasminogen activator via cross-collaterals may also lead to clinical recovery without avoiding the need for stenting [51]. Therefore, the combination of IV and IA thrombolysis may be particularly beneficial in distal ICA occlusion as indicated by Zaidat et al. [52]. In comparison, mechanical and/ or pharmacological IA thrombolysis with stent implantation in the proximal segment of the ICA had higher bleeding and mortality rates [53]. Conversely, in patients undergoing endovascular treatment arterial reocclusion and distal embolization occurred in 16–18% resulting in poor long-term outcome [54]. A meta-analysis of studies including IV or IA therapy options in ischemic stroke due to ICA occlusion showed a strong association between recanalization rates and improved functional outcome [55]. Recanalization was associated with better outcome, and recanalization rates with mechanical techniques were higher to merely pharmacological recanalization therapy [56]. Further, an overview of 28 studies with 385 patients in the IV thrombolysis group and 584 in the endovascular group pointed out that endovascular treatment of acute ICA occlusion resulted in improved clinical outcome compared with the IV thrombolysis-treated group [57].

Review

There are two main approaches: the retrojugular and the ventrojugular access of which the latter is the most common access route. The retrojugular approach was developed because of the possibility of higher exposure of the ICA without mobilization of the hypoglossal nerve, shorter operating times and favorable cosmetic results [58]. In a prospective randomized single-center study the comparability of both approaches was tested [59]. The study was stopped after an interim analysis, due to an increase of a temporary ipsilateral vocal cord dysfunction in the retrojugular approach (31 vs 6%, p = 0.0014). The acute occlusion of the ICA is only approachable for the surgeon, if the thrombus does not exceed the skull base [60]. In these selected patients, an operation with classical CEA with/ without a Fogarty maneuver is possible. The indications are the same as for urgent CEA (exclusion of a disabling neurologic deficit, cerebral lesions >3 cm or one-third of the MCA perfusion area, intracerebral hemorrhage) [61]. Similarly, emergency ICA surgery was found to be effective and safe when performed within 48 h [35]. In a prospective single-center study, over a time period of 10 years the primary patency at discharge was 78%, perioperative cerebral event rate (stroke, intracranial hemorrhage) was 43%, while only 47% of the patients showed an improvement in the modified Rankin scale. These results are time dependent. Subgroup analysis showed significant better results in patients operated within 72 h of onset of the neurological event [62]. Similar results were given by Benesˇ et al. [60] and Kasper et al. [63]. The recanalization rates were about 80% and secondary hemorrhage about 5% [60]. Appropriate selection of the patients in the correct timeframe is crucial [64]. Specifically, CEA performed within 7–13 days following systemic thrombolysis is safe as found in 22 patients who were followed for 30 days [65]. In a further small series, similar findings were obtained when carotid surgery followed systemic thrombolysis between 6 and 45 h [66]. This was also evident from a third study when patients were operated on average 6 days after thrombolysis and followed for 3 months [67,68]. A particular and rare condition is the carotid pseudo-occlusion, which can occur with the symptoms of an acute ICA occlusion or it can be seen in asymptomatic patients. It is characterized in DSA by a severely reduced antegrade flow into the ICA with a string-like filling (string sign or slim sign) or retrograde filling up to the skull base in the late phase of angiography [28]. Since its first description in 1970, non-invasive imaging has been improved and now leads to more valid assessment [29]. Only a few retrospective studies exist about the surgical treatment of carotid pseudo-occlusion. The perioperative stroke rate ranges from 2.5 to 11.8%, with a mortality rate between 1.9 and 10%. Patency rates were 75.5–79% [32,34]. ICA occlusion due to dissection

Surgery in acute ICA (pseudo-)occlusion

In CEA, the arteriosclerotic plaque at the carotid bifurcation and the thrombotic material causing the obstruction of the ICA is removed surgically. The carotid bifurcation gets prepared via a cervical longitudinal or horizontal skin incision. informahealthcare.com

The annual incidence of the spontaneous extracranial ICA dissection is approximately 2.5–3/100,000 [69,70]. The risk of a stroke after an extracranial internal cerebral artery dissection (ICAD) is considered very high and approaches 70% [71]. Dissections arise from a hematoma in the vascular wall. Hemorrhage doi: 10.1586/14737175.2014.955477


Review


of the vasa vasorum between the middle coat and adventitia of the arterial wall probably causes the extracranial dissections [72]. Spontaneous dissection typically occurs without any trigger or after minimal trauma [70,73,74]. Notably, extracranial dissections can expand occasionally into the intracranial cavity, or intracranial dissections can develop primarily in the subarachnoid space [23]. They bear an increased risk of a subarachnoid hemorrhage (SAH). Thus, anticoagulation is not recommended in these latter cases [75–77]. If intracranial dissections are associated with SAH and ruptured fusiform dissecting aneurysm, then interventional therapy or operation of the aneurysm has priority [78]. For acute ischemic stroke caused by ICAD, there are no controlled randomized trials that have investigated the safety and efficacy of systemic thrombolysis or interventional recanalization. [79]. All currently available data on this topic is based on observational studies or case reports. Intravenous thrombolysis within the 4.5 h time window appears to be possible without specifically elevated risk in patients with spontaneous ICAD (sICAD) and ischemic stroke [79,80]. Patients with ischemic stroke due to sICAD were not excluded in any controlled, randomized intravenous thrombolysis therapy trial, which evaluated the effect of tissue plasminogen activator in ischemic stroke [81–84]. A review [79] collected four studies with 50 patients who had sICAD causing ischemic stroke treated with intravenous thrombolysis [85–87]. There was no evidence of clinical deterioration, rupture of the dissected artery or SAH [85–87]. In a retrospective IV thrombolysis therapy study, the risk of ischemic stroke patients with ICA dissection to suffer an intracranial hemorrhage (incidence 14.5%) was not elevated compared with patients with other stroke etiology (incidence 14.2%) [88]. A meta-analysis on the rate of symptomatic intracranial bleeding and of good clinical outcome did not show a difference in patients with dissection who were treated with IV thrombolysis (n = 121) compared with IA thrombolysis (n = 59) or with other stroke etiologies [89]. But the complication rates were similar across the patient groups. Endovascular or surgical treatments are normally not recommended in acute therapy for spontaneous ICAD, as the risk of recurrent ischemic strokes under optimal conservative treatment seems to be low and is only poorly associated with residual occlusion/stenosis [90] or dissecting aneurysms [91,92]. These treatments are invasive and therefore should be restricted to exceptional cases [93]. In fact, endovascular therapy of dissection is technically challenging and an unsuccessful trial of endovascular recanalization may impede natural healing and recanalization. However, hemodynamic failure or thromboembolic events despite effective pharmacologic therapy could be an indication for interventional endovascular treatment in such circumstances [94]. However, in case of recurrent ischemic strokes under optimal conservative treatment or upon hemodynamic decompensation, interventional treatment with or without stent implantation can be considered in individual paients. There are only small case series regarding this issue [95]. In a group with stent application in the ICA (n = 26) [96] or in a small group doi: 10.1586/14737175.2014.955477

of patients (n = 6) with stent-assisted thrombolysis with bolus injection of Gp IIb/IIIa antagonists and mechanical thrombectomy [97], there were no higher rates of complications. In ICA dissection, medical treatment rather than interventional or surgical treatment is recommended in most stroke centers. Antiplatelet medication, usually aspirin, and anticoagulation are used either for primary or secondary stroke prevention in ICAD. Empirical arguments for antiplatelet treatment may be severe stroke with large infarction, accompanying intracranial dissection, local compression syndromes without ischemic events or concomitant diseases with increased bleeding risk. In turn, (pseudo-)occlusion of the dissected artery, high-intensity transient signals in transcranial ultrasound studies despite (dual) antiplatelets, multiple ischemic events in the same circulation or visualization of free-floating thrombus may favor anticoagulation [77]. However, no randomized trial has yet been done to compare the efficacy of the two treatments. Non-randomized trials, a meta-analysis and a Cochrane systematic meta-analysis have shown no significant difference regarding recurrent stroke risk and risk of death between the two treatments in ICAD [98,99]. Recurrent ischemic events in ICAD are regarded to be rare. However, the rate of recurrent ischemic strokes has been estimated to be between 0% [69] and 13.3% [100] at 1 year. Recurrences usually happen in the first weeks after the dissection [100,101]. Multiple dissections [101] and a history of hypertension [100] are associated with an elevated risk. A few cases reported that chronic dissecting aneurysms of the carotid artery caused ischemic strokes [102,103]. But two prospective series of aneurysmal ICAD showed no ischemic stroke after a followup period of about 3 years [91,92]. In another long-term followup of 130 patients with ICAD, ischemic recurrences were associated with worsening of carotid stenosis in five of six cases [104]. The optimal duration of antithrombotic treatment is unclear, spontaneous recanalization of ICA occlusions at a later time point is common and may lead to further neurological events as found in a follow-up study over up to more than 100 months [105]. The recanalization can be monitored with Duplex sonography. After ICA dissection, remodeling of the thrombotic material in the ICA has been found to occur for up to 2 years [106]. Follow-up visits and follow-up imaging is, therefore, recommended to guide the treatment period. Anticoagulants are usually prescribed for no longer than 6 months. Long-term prevention of cerebral ischemia with antiplatelet drugs can be discussed based on the overall vascular risk profile of the patients, as well as on empirical considerations in cases of residual stenosis, occlusion or aneurysm, even though these patients have not been proven to have an increased risk of stroke recurrence. But as an observational study in 250 patients showed a relatively high cumulative recurrent stroke rate during the first year of 10.7 and 14.0% over 3 years [107], a long-term treatment with antiplatelet drugs in case of an ischemic stroke due to a dissection despite recanalized dissection can be considered for secondary stroke prevention. Recent evidence also indicates that hypertension, although less prevalent than in patients Expert Rev. Neurother.



with a non-ICAD ischemic stroke, could be a risk factor for ICAD [108]. Careful monitoring and treatment of hypertension is therefore mandatory in ICAD patients. Recurrences of dissections seem to be rare; they seem to be most frequent within the first 2 months after the initial event [109]. Recurrent dissections were not reported in the only population-based study with follow-up of 48 patients with ICAD (mean duration of follow-up: 7.8 years) [69]. Further series describe the rate of recurrent dissections to be between 0 [101] and 25% [109]. Patients have a higher risk of recurrent ICAD, if they have younger age [110], a family history of ICAD [111], vascular Ehlers-Danlos syndrome [112], or fibromuscular dysplasia [112–114]. The prognosis of recurrent ICAD is considered as good [109]. An underlying monogenic connective tissue disease, such as vascular Ehlers-Danlos syndrome, might require specific treatments and preventive measures [115] [112]. Patients with young age, an underlying connective tissue disorder, a family history of ICAD or fibromuscular dysplasia are recommended to have longer and more frequent follow-ups, because of increased risk of ICAD recurrence [74,110–114]. In most instances, recanalization of sICAD occurs within the first months after manifestation [116] [117]. At later stages, only few cases of delayed recanalization have been described [117]. There is only one non-controlled observational long-term follow-up study, which investigated the rate of ischemic strokes and intracranial hemorrhage in persistent (n = 46) and transient (n = 46) severe stenosis or occlusion of the ICA due to unilateral sICAD [90]. Antithrombotic therapy and follow-up were similar in the permanent (6.2 ± 3.4 years) and transient (7.2 ± 4.3 years) severe stenosis or occlusion of the ICA group, although the therapy was administered at the discretion of the treating physician. Both groups showed low risks of recurrent ischemic stroke. Patients with permanent carotid obstruction showed low risk of strokes with annual rates of 0.7% for ipsilateral carotid territory stroke and only 1.4% for any stroke, whereas patients in the transient carotid obstruction group showed similar small annual rates of 0.3% for ipsilateral carotid territory stroke and 0.6% for any stroke [90]. Chronic ICA occlusion

A chronic occlusion of the ICA typically develops on the basis of a progressive arteriosclerotic stenosis at the ICA bifurcation. Hemorrhagic changes of the arteriosclerotic plaque can induce a rapid progress of the degree of stenosis and are predictive of imminent stroke [118]. But usually the reduction of blood supply in the perfusion territory of the ICA due to such a progressive ICA stenosis is compensated by extracranial-intracranial (EC/IC) and intracranial collaterals (FIGURE 3). Consequently, the carotid stenosis may remain clinically asymptomatic even in high-grade and subtotal ICA stenoses. In fact, many patients may present with an ICA occlusion, which is found incidentally upon screening examinations of the cerebral arteries. The development of extracranial carotid artery stenosis may not be limited to one side, but may affect the carotid artery in a bilateral fashion. Again the progress of the disease is typically slowly informahealthcare.com

Review

progressive and asymmetric. This may lead in rare instances to a bilateral asymptomatic occlusion of the ICA. In such a situation, collaterals fed by the vertebrobasilar arteries have taken over the blood supply of the brain. In essence, the classification of an ICA occlusion as chronic is retrospective, since it describes the vessel occlusion in absence of a neurological event. Typically, MRI shows a severe delay of brain perfusion in the ICA territory but with a normal regional CBV and without changes of diffusion-weighted imaging [11,12]. The delay of perfusion can be substantial, for example, 6 s or more in comparison to the non-affected cerebral hemisphere, but the amount of arterial blood is sufficient to meet the needs of the brain. It is not known if the recruitment of collaterals can go ahead with a normal cerebral blood volume in the presence of a delay of cerebral perfusion as demonstrated in TTP and Tmax maps [119]. Nevertheless, the cerebrovascular perfusion reserve may become affected when in presence of an ICA occlusion the intracranial collaterals become insufficient owing to arteriosclerosis. A reduced cerebrovascular perfusion reserve is associated with an increased risk of ischemic events [120]. In fact, a chronic ICA occlusion bears a considerable risk of ipsilateral ischemic stroke. In a 7-year follow-up study, it was found that 86% of ischemic events were attributable to the occluded ICA [121]. Furthermore, in normal appearing brain tissue microstructural changes as identified with DWI predict a decline in psychomotor speed, executive functions and working memory, which were found to be related to functional disability and higher mortality [122]. EC/IC bypass in chronic ICA occlusion?

For approximately 50 years, EC/IC bypass surgery has been suggested as a therapeutic option in symptomatic ICA occlusions. EC/IC bypass surgery is an operative procedure, which most commonly involves the anastomosis of the superficial temporal artery to the MCA (bypass), mainly to overcome an intracranial carotid and/or MCA occlusion (FIGURE 4). The results of the first EC/IC bypass surgery were published by Donaghy and Yasargil in 1967 and 1969, after which this method was performed increasingly in the next decades. To assess the efficacy of EC/IC bypass surgery compared with conservative or medical treatment, a large, prospective multicenter trial randomizing 1377 patients either to medical or surgical therapy was initiated. The results of the EC/IC Bypass Study did not demonstrate a benefit of EC/IC bypass surgery over medical therapy in patients with symptomatic carotid occlusion [123]. In detail, 29% of the medically treated patients experienced one or more strokes, compared with 31% of patients in the surgically treated group. In more recent years, the North American Carotid Occlusion Surgery Study (COSS) and the Japanese EC-IC Bypass Trial set out using highly elaborated study designs to evaluate the role of EC/IC bypass surgery for treatment of chronic cerebral ischemia. This included multifactorial hemodynamic brain imaging of the perfusion reserve, which is assessed by hypercapnia induced by IV application of carboanhydrase (FIGURE 4). The main objective of these trials was to elucidate whether EC/IC bypass surgery in addition to best medical treatment versus best doi: 10.1586/14737175.2014.955477

Review


80

350

A

MTT pre Tmax pre MTT post Tmax post CBF pre CBV pre CBF post CBVpost

70

300

60

50 200 40 150 30 100 20

50

10

0

0

AC ACPre ACPre ACPre HGPre HGZre HGZre AC Zre ACMre ACMre ACMre ACMre ACMre ACMre ACMre ACMre ACMre ACMre VGMre VGZre AC Zre ACAre ACAre A AC re ACAll VGAll VGZll VGZll AC Zll ACMll ACMll ACMll ACMll ACMll ACMll ACMll ACMll ACMll ACMll HGMll HGZll HGZll AC Zll ACPll ACPll Pl l


250

STA (parietal branch)

B

Craniotomy

STA (frontal branch)

Occlusion

Figure 4. Information for extra-intracranial bypass surgery. (A) Multiparametric imaging: cross-sectional representation of parameters of cerebral perfusion before and after administration of carboanhydrase in order to assess the cerebral perfusion reserve. Normal symmetric response in both cerebral hemispheres as shown by the increase of the MTT, Tmax, regional CBF and regional CBV. Ordinate with relative signal intensity, abscissa showing the different regions of data sampling. (B) Arteries important for extracranial-intracranial operation. CBF: Cerebral blood flow; CBV: Cerebral blood flow; MTT: Mean transit time; STA: Superficial temporal artery; Tmax: Peak of the contrast bolus. Data taken from [132].

doi: 10.1586/14737175.2014.955477




medical treatment alone could reduce the risk of subsequent ipsilateral stroke, improve cerebral hemodynamics, and importantly reduce disability after stroke. EC/IC bypass surgery in ICA surgery is associated with more than a 15% rate of ipsilateral ischemic stroke, although vessel patency was demonstrated in 90% of patients [124,125]. Recently, position statements by the Joint Cerebrovascular Section of the American Association of Neurological Surgeons and Congress of Neurological Surgeons and by the Cerebrovascular Section of the European Association of Neurosurgeons were developed to address some of the shortcomings of the COSS study [126,127]. They were phrased in consideration of the following observations. The sample-size calculation of the COSS study was based on the Saint Louis Carotid Occlusion Study (STLCOS) data. It was estimated to require a total of 372 patients [128]. The primary outcome was defined as all strokes and death within 30 days after surgery and ipsilateral ischemic stroke within 2 years. Based on an interim analysis, the study was halted after randomization of 195 patients. The reasons were: • The 30-day event rate in the surgical group was about 14.4%; • The 2-year outcome rate did not differ significantly between the surgical (21%) and the medical group (22.7%). Notably, the risk of stroke in the medical group was significantly lower than projected by the STILCOS data (22.7% instead of 40%). This lower incidence of stroke was mainly explained through improvement of medical therapy, especially due to the increased use of statins [129]. It has to be emphasized that the observed risk reduction of 17% in the conservative group of COSS cannot solely be explained through intensified medical management, since even the Stroke Prevention by Aggressive Reduction in Cholesterol Levels study demonstrated an absolute risk reduction of only 5% due to the use of statins [130,131]. • Furthermore, the perioperative morbidity of COSS appeared to be high, especially since one would expect an improvement of surgical standard compared with the state of the art 25 years ago. In our opinion, the 2-year-follow-up provided a clear benefit for patients within the surgically treated group, once the 30-day perioperative period had passed without an additional ischemic event [132]. Thus, COSS was prematurely stopped due to a futility analysis based on the original effect size calculation. However, although a positive effect of bypass surgery using a modified risk difference was seen, an extension of the study with an increased sample size was probably considered to be complex and costly. Medical treatment in ICA occlusion

In European countries, aspirin in a dose of 100 mg once daily is used for secondary prevention after ischemic stroke or TIA to reduce the risk of myocardial infarction, stroke or vascular death [133,134]. Alternatively, a combination of aspirin and dipyridamol or clopidogrel can be used [135–141]. This secondary prevention after ischemic stroke or TIA with antiplatelets is usually informahealthcare.com

Review

also applied in patients with stable ICA occlusion. If there is a symptomatic extracranial ICA stenosis other approaches of secondary prevention may be assumed, which are not the subject of this article [142–149]. It should be pointed out, however, that in patients with recently symptomatic carotid stenosis, combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing asymptomatic embolization measured by Doppler microembolic signal detection [150]. In addition, recent studies have shown that the combined treatment of aspirin and clopidogrel for a temporary period of 3 months in certain indications, for example, symptomatic intracranial arterial stenosis [131] or after TIA or minor stroke in a Chinese population [151] have a beneficial effect in stroke prevention. But in clinical end points, the combination of clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infarction, stroke or death from cardiovascular causes over a period of more than 2 years [152]. Furthermore, the combined treatment over 18 months in high-risk patients with recent ischemic stroke or TIA had no significant effect in reducing major vascular events compared with clopidogrel alone. In addition, the risk of life-threatening or major bleeding was increased in the combination therapy [153]. Thus, there is evidence that the combined treatment is beneficial in secondary stroke prevention for a period of approximately 3 months in certain indications and should be de-escalated to aspirin or clopidogrel after the period to reduce the hemorrhage risk. Other oral antiplatelet substances which have been introduced into cardiology have no approval for the acute treatment of stroke so far. However, there are liquid platelet receptor antagonists that may be of help in the intravenous treatment of acute stroke with a duration of administration of 48–72 h [154,155]. But these intravenous platelet inhibitors have not been studied in prospective randomized and blinded trials in ischemic stroke. Expert commentary

A fast and proper interdisciplinary assessment of the underlying vascular pathology and the cerebrovascular risk factors is required for an optimal management of the patients with ICA occlusion syndromes. Symptomatic acute ICA occlusion is a potentially devastating condition. Patient management involves careful history taking, proper neurological examination and the adequate selection of diagnostic procedures including CTA, MRA and DSA techniques as well as multimodal brain imaging. Invasive intervention options available at dedicated stroke centers are to be tailored for the individual patient in an interdisciplinary fashion and weighed against or in combination with medical treatment. Both, diagnostic precision and the therapeutic measures are the most important prognostic factor for clinical stabilization and long-term outcome. Because of availability and matter of approval, IV thrombolysis is the first-line therapy in ischemic stroke due to symptomatic ICA occlusion, although recanalization rates are rather limited and clinical outcome is often poor. There is evolving evidence for the beneficial effect of endovascular treatment in specialized stroke centers with mechanical thrombectomy and/or stenting doi: 10.1586/14737175.2014.955477


Review


with or without systemic thrombolysis. For the time being, interventional endovascular treatment approaches with constantly changing materials are heterogeneous and may include IA thrombolysis, microwire clot disruption, angioplasty, thromboaspiration, stenting and thrombectomy with stent retrievers or MERCI retrievers. Therefore, prospective randomized controlled trials are needed to assess the efficacy of interventional endovascular therapy including thrombectomy and stenting. Also, there is general agreement that after good selection, there is a benefit for emergency CEA of a pseudo-occlusion of the ICA. Because of the low incidence (largest series with 128 patients over a 13-year period [34]), however, there is no recommendation for this intervention in the national or international guidelines. The results of a large, single follow-up study indicate that sICAD has a benign long-term prognosis with low rates of ipsilateral carotid territory and any stroke, and that the stroke rate in sICAD is not related to the persistence of severe carotid stenosis or occlusion. Accordingly, with the limitation of only a single study, conservative treatment with antithrombotic agents seems to be sufficient in most patients with sICAD causing severe stenosis or occlusion [90]. Controlled studies are needed to investigate the potential efficacy and safety of interventional treatment in stroke due to ICAD. Non-randomized trials, a meta-analysis and a Cochrane systematic meta-analysis have shown that there is no difference between anticoagulation and antiplatelets in recurrent risk of stroke or risk of death [98,99]. Therefore, at

present empirical arguments are used to decide between anticoagulants or antiplatelet drugs, and the decision should be made on an individual risk profile. There is a tendency in many centers to advise anticoagulation for a limited period, typically 6 months, in ICA dissection with or without occlusion. Asymptomatic ICA occlusion, usually detected as an instant finding, is usually managed with antiplatelet medication using 100 mg aspirin/day and follow-up of the other brain supplying arteries using Doppler and Duplex sonography. Five-year view

Given the relatively low number of patients with symptomatic carotid artery occlusion, prospective registries are mandatory to provide criteria for triaging patients into medical versus surgical or interventional treatment pathways. The rapid developments in stent retriever technology will offer new options for recanalization of acute ICA occlusions, restoration of cerebral reperfusion and favorable clinical outcome. Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties. No writing assistance was utilized in the production of this manuscript.

Key issues • Rapid multimodal imaging of the cerebral arteries, of the cerebral hemodynamics and of brain water diffusion is required for assessing the potential risk of an internal carotid artery (ICA) occlusion for subsequent manifestation of an ischemic stroke. • The pathogenesis underlying an ICA occlusion in a given patient is an important prognostic factor for patient outcome. • ICA dissection is a severe disorder, particularly when associated with large embolic territorial brain infarction. • Systemic thrombolysis often fails to induce rapid recanalization in acute ICA additional occlusion, which typically goes along with an occlusion of an intracranial carotid T occlusion. • Surgical and especially interventional therapeutic approaches have been shown to be suited for rapid ICA recanalization within 48 h after symptom onset. They need to be compared regarding recanalization rate, long-term efficacy and safety. • Medical treatment typically relies on platelet aggregation inhibitors in chronic ICA occlusions. • A chronic ICA occlusion enhances the risk of interventions on a symptomatic process of the contralateral ICA. • Extracranial-intracranial bypass surgery appears attractive, but has not been proven to be beneficial in chronic ICA occlusion even in highly selected patients who were subjected to modern multimodal imaging.

References 1.

Amarenco P, Bogousslavsky J, Caplan LR, et al. New approach to stroke subtyping: the A-S-C-O (phenotypic) classification of stroke. Cerebrovasc Dis 2009;27(5):502-8

2.

Miller VT. Lacunar stroke. a reassessment. Arch Neurol 1983;40(3):129-34

3.

Boiten J, Lodder J. Lacunar infarcts. Pathogenesis and validity of the clinical syndromes. Stroke 1991;22(11):1374-8

doi: 10.1586/14737175.2014.955477

4.

Seitz RJ, Donnan GA. Role of neuroimaging in promoting long-term recovery from ischemic stroke. J Magn Reson Imaging 2010;32(4):756-72

5.

Campbell BC, Christensen S, Parsons MW, et al. Advanced imaging improves prediction of hemorrhage after stroke thrombolysis. Ann Neurol 2013;73(4):510-19

6.

Amarenco P, Ro¨ther J, Michel P, et al. Aortic arch atheroma and the risk of stroke. Curr Atheroscler Rep 2006;8(4):343-6

7.

Antoniou GA, Kuhan G, Sfyroeras GS, et al. Contralateral occlusion of the internal carotid artery increases the risk of patients undergoing carotid endarterectomy. J Vasc Surg 2013;57(4):1134-45

8.

Seitz RJ, Meisel S, Weller P, et al. Initial ischemic event: perfusion-weighted MR imaging and apparent diffusion coefficient for stroke evolution. Radiology 2005; 237(3):1020-8

9.

Albers GW, Thijs VN, Wechsler L, et al. Magnetic resonance imaging profiles predict



clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study. Ann Neurol 2006;60(5): 508-17


10.

11.

12.

13.

14.

Olivot JM, Mlynash M, Thijs VN, et al. Relationships between infarct growth, clinical outcome, and early recanalization in diffusion and perfusion imaging for understanding stroke evolution (DEFUSE). Stroke 2008;39(8):2257-63 Surikova I, Meisel S, Siebler M, et al. Significance of the perfusion-diffusion mismatch in chronic cerebral ischemia. J Magn Reson Imaging 2006;24(4):771-8 Liebeskind DS, Cotsonis GA, Saver JL, et al. Collaterals dramatically alter stroke risk in intracranial atherosclerosis. Ann Neurol 2011;69(6):963-74 Hussain MS, Lin R, Cheng-Ching E, et al. Endovascular treatment of carotid embolic occlusions has a higher recanalization rate compared with cardioembolic occlusions. J Neurointerv Surg 2010;2(1):71-3 Byrnes KR, Ross CB. The current role of carotid duplex ultrasonography in the management of carotid atherosclerosis: foundations and advances. Int J Vasc Med 2012;2012:187872

15.

Quirk K, Bandyk DF. Interpretation of carotid duplex testing. Semin Vasc Surg 2013;26(2-3):72-85

16.

Hofstee DJ, Hoogland PH, Schimsheimer RJ, de Weerd AW. Contrast enhanced color duplex for diagnosis of subtotal stenosis or occlusion of the internal carotid artery. Clin Neurol Neurosurg 2000; 102(1):9-12

17.

Willinsky RA, Taylor SM, TerBrugge K, et al. Neurologic complications of cerebral angiography: prospective analysis of 2,899 procedures and review of the literature. Radiology 2003;227(2):522-8

18.

Debrey SM, Yu H, Lynch JK, et al. Diagnostic accuracy of magnetic resonance angiography for internal carotid artery disease: a systematic review and meta-analysis. Stroke 2008;39(8):2237-48

19.

Schreiber S, Schreiber F, Glaser M, et al. Detecting artery occlusion and critical flow diminution in the case of an acute ischemic stroke–methodological pitfalls of common vascular diagnostic methods. Ultraschall Med 2011:32(3):274-80

20.

Marquering HA, Nederkoorn PJ, Beenen LF, et al. Carotid pseudo-occlusion on CTA in patients with acute ischemic stroke: a concerning observation. Clin Neurol Neurosurg 2013;115(9):1591-4


21.

De Silva DA, Fink JN, Christensen S, et al. Assessing reperfusion and recanalization as markers of clinical outcomes after intravenous thrombolysis in the echoplanar imaging thrombolytic evaluation trial (EPITHET). Stroke 2009;40(8):2872-4

22.

Ogata T, Nagakane Y, Christensen S, et al. A topographic study of the evolution of the MR DWI/PWI mismatch pattern and its clinical impact: a study by the EPITHET and DEFUSE Investigators. Stroke 2011; 42(6):1596-601

23.

Olivot J-M, Mlynash M, Thijs VN, et al. Optimal Tmax threshold for predicting penumbral tissue in acute stroke. Stroke 2009;40(2):469-75

24.

Ogata T, Christensen S, Nagakane Y, et al. The effects of alteplase 3 to 6 hours after stroke in the EPITHET-DEFUSE combined dataset: post hoc case-control study. Stroke 2013;44(1):87-93

25.

26.

27.

28.

Sakamoto Y, Sato S, Kuronuma Y, et al. Factors associated with proximal carotid axis occlusion in patients with acute stroke and atrial fibrillation. J Stroke Cerebrovasc Dis 2014(23):5:799-804 Rubiera M, Ribo M, Delgado-Mederos R, et al. Tandem internal carotid artery/middle cerebral artery occlusion: an independent predictor of poor outcome after systemic thrombolysis. Stroke 2006;37(9):2301-5 Westein E, van der Meer AD, Kuijpers MJ, et al. Atherosclerotic geometries exacerbate pathological thrombus formation poststenosis in a von Willebrand factor-dependent manner. Proc Natl Acad Sci USA 2013;110(4):1357-62 Bowman JN, Olin JW, Teodorescu VJ, et al. Carotid artery pseudo-occlusion: does end-diastolic velocity suggest need for treatment? Vasc Endovascular Surg 2009; 43(4):374-8

29.

Ascher E, Markevich N, Hingorani A, Kallakuri S. Pseudo-occlusions of the internal carotid artery: a rationale for treatment on the basis of a modified carotid duplex scan protocol. J Vasc Surg 2002; 35(2):340-5

30.

Inoue T, Tamura A, Tsutsumi K, et al. Surgical embolectomy for large vessel occlusion of anterior circulation. Br J Neurosurg 2013;27(6):783-90

31.

Camerlingo M, Tudose V, Tognozzi M, Moschini L. Predictors of recanalisation in acute cerebral infarction from occlusion of the terminal internal carotid artery or of the middle cerebral artery main stem treated with thrombolysis. Int J Neurosci 2014; 124(3):199-203

Review

32.

Greiner C, Wassmann H, Palkovic S, Gauss C. Revascularization procedures in internal carotid artery pseudo-occlusion. Acta Neurochir (Wien) 2004;146(3):237-43; discussion 243

33.

Ogata T, Yasaka M, Kanazawa Y, et al. Outcomes associated with carotid pseudo-occlusion. Cerebrovasc Dis 2011; 31(5):494-8

34.

Kniemeyer HW, Aulich A, Schlachetzki F, et al. Pseudo- and segmental occlusion of the internal carotid artery: a new classification, surgical treatment and results. Eur J Vasc Endovasc Surg 1996;12(3): 310-20

35.

Huber R, Mu¨ller BT, Seitz RJ, et al. Carotid surgery in acute symptomatic patients. Eur J Vasc Endovasc Surg 2003; 25(1):60-7

36.

Meyer FB, Sundt TM Jr, Piepgras DG, et al. Emergency carotid endarterectomy for patients with acute carotid occlusion and profound neurological deficits. Ann Surg 1986;203(1):82-9

37.

Smith WS, Lev MH, English JD, et al. Significance of large vessel intracranial occlusion causing acute ischemic stroke and TIA. Stroke 2009;40(12):3834-40

38.

Zivanovic Z, Gvozdenovic S, Jovanovic DR, et al. Intravenous thrombolysis in acute ischemic stroke due to occlusion of internal carotid artery - A Serbian Experience with Thrombolysis in Ischemic Stroke (SETIS). Clin Neurol Neurosurg 2014;120:124-8

39.

Paciaroni M, Agnelli G, Caso V, et al. Intravenous thrombolysis for acute ischemic stroke associated to extracranial internal carotid artery occlusion: the ICARO-2 study. Cerebrovasc Dis 2012; 34(5-6):430-5

40.

Adams HP Jr, del Zoppo G, Alberts MJ, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/ American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke 2007;38(5):1655-711

41.

Seet RC, Wijdicks EF, Rabinstein AA. Stroke from acute cervical internal carotid artery occlusion: treatment results and predictors of outcome. Arch Neurol 2012; 69(12):1615-20

doi: 10.1586/14737175.2014.955477

Review 42.

Del Zoppo GJ, Poeck K, Pessin MS, et al. Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol 1992;32(1):78-86

43.

Jansen O, von Kummer R, Forsting M, et al. Thrombolytic therapy in acute occlusion of the intracranial internal carotid artery bifurcation. AJNR Am J Neuroradiol 1995;16(10):1977-86

44.



45.

46.

47.

48.

49.

50.

51.

52.

Lee K-Y, Han SW, Kim SH, et al. Early recanalization after intravenous administration of recombinant tissue plasminogen activator as assessed by preand post-thrombolytic angiography in acute ischemic stroke patients. Stroke 2007;38(1): 192-3 Pechlaner R, Knoflach M, Matosevic B, et al. Recanalization of extracranial internal carotid artery occlusion after i.v. thrombolysis for acute ischemic stroke. PLoS One 2013;8(1):e55318 De Silva DA, Brekenfeld C, Ebinger M, et al. The benefits of intravenous thrombolysis relate to the site of baseline arterial occlusion in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET). Stroke 2010;41(2):295-9 Paciaroni M, Balucani C, Agnelli G, et al. Systemic thrombolysis in patients with acute ischemic stroke and Internal Carotid ARtery Occlusion: the ICARO study. Stroke 2012; 43(1):125-30

53.

Nedeltchev K, Brekenfeld C, Remonda L, et al. Internal carotid artery stent implantation in 25 patients with acute stroke: preliminary results. Radiology 2005; 237(3):1029-37

65.

Rathenborg LK, Jensen LP, Baekgaard N, Schroeder TV. Carotid endarterectomy after intravenous thrombolysis for acute cerebral ischaemic attack: is it safe? Eur J Vasc Endovasc Surg 2013;45(6):573-7

54.

Janjua N, Alkawi A, Suri MF, Qureshi AI. Impact of arterial reocclusion and distal fragmentation during thrombolysis among patients with acute ischemic stroke. AJNR Am J Neuroradiol 2008;29(2):253-8

66.

55.

Rha JH, Saver JL. The impact of recanalization on ischemic stroke outcome: a meta-analysis. Stroke 2007;38(3):967-73

McPherson CM, Woo D, Cohen PL, et al. Early carotid endarterectomy for critical carotid artery stenosis after thrombolysis therapy in acute ischemic stroke in the middle cerebral artery. Stroke 2001;32(9): 2075-80

67.

Fischer U, Mono ML, Schroth G, et al. Endovascular therapy in 201 patients with acute symptomatic occlusion of the internal carotid artery. Eur J Neurol 2013;20(7): 1017-24.e87

Crozier JEM, Reid J, Welch GH, et al. Early carotid endarterectomy following thrombolysis in the hyperacute treatment of stroke. Br J Surg 2011;98(2):235-8

68.

Leseche G, Alsac J-M, Houbbalah R, et al. Carotid endarterectomy in the acute phase of stroke-in-evolution is safe and effective in selected patients. J Vasc Surg 2012;55(3): 701-7

69.

Lee VH, Brown RD Jr, Mandrekar JN, Mokri B. Incidence and outcome of cervical artery dissection: a population-based study. Neurology 2006;67(10):1809-12

70.

Schievink WI. Spontaneous dissection of the carotid and vertebral arteries. N Engl J Med 2001;344(12):898-906

71.

Baumgartner RW, Arnold M, Baumgartner I, et al. Carotid dissection with and without ischemic events: local symptoms and cerebral artery findings. Neurology 2001;57(5):827-32

72.

Vo¨lker W, Dittrich R, Grewe S, et al. The outer arterial wall layers are primarily affected in spontaneous cervical artery dissection. Neurology 2011;76(17):1463-71

73.

Dittrich R, Rohsbach D, Heidbreder A, et al. Mild mechanical traumas are possible risk factors for cervical artery dissection. Cerebrovasc Dis 2007;23(4):275-81

74.

Debette S, Leys D. Cervical-artery dissections: predisposing factors, diagnosis, and outcome. Lancet Neurol 2009;8(7): 668-78

75.

Guillon B, Le´vy C, Bousser MG. Internal carotid artery dissection: an update. J Neurol Sci 1998;153(2):146-58

76.

Chen M, Caplan L. Intracranial dissections. Front Neurol Neurosci 2005;20:160-73

77.

Engelter ST, Brandt T, Debette S, et al. Antiplatelets versus anticoagulation in cervical artery dissection. Stroke 2007;38(9): 2605-11

78.

Metso TM, Metso AJ, Helenius J, et al. Prognosis and safety of anticoagulation in intracranial artery dissections in adults. Stroke 2007;38(6):1837-42

56.

57.

58.

Safar HA, Doobay B, Evans G, et al. Retrojugular approach for carotid endarterectomy: a prospective cohort study. J Vasc Surg 2002;35(4):737-40

59.

Stehr A, Scodacek D, Wustrack H, et al. Retrojugular versus ventrojugular approach to carotid bifurcation for eversion endarterectomy: a prospective randomized trial. Eur J Vasc Endovasc Surg 2008;35(2): 190-5.discussion 196-197

Kappelhof M, Marquering HA, Berkhemer OA, Majoie CB. Intra-arterial treatment of patients with acute ischemic stroke and internal carotid artery occlusion: a literature review. J Neurointerv Surg 2014. [Epub ahead of print]

60.

Ratanaprasatporn L, Grossberg JA, Spader HS, Jayaraman MV. Endovascular treatment of acute carotid occlusion. Clin Neurol Neurosurg 2013;115(12):2521-3

61.

Yoon YH, Yoon W, Jung MY, et al. Outcome of mechanical thrombectomy with Solitaire stent as first-line intra-arterial treatment in intracranial internal carotid artery occlusion. Neuroradiology 2013; 55(8):999-1005 Bulsara KR, Ediriwickrema A, Pepper J, et al. Tissue plasminogen activator via cross-collateralization for tandem internal carotid and middle cerebral artery occlusion. World J Clin Cases 2013;1(9):290-4 Zaidat OO, Suarez JI, Santillan C, et al. Response to intra-arterial and combined intravenous and intra-arterial thrombolytic therapy in patients with distal internal carotid artery occlusion. Stroke 2002;33(7): 1821-6

doi: 10.1586/14737175.2014.955477

Mokin M, Kass-Hout T, Kass-Hout O, et al. Intravenous thrombolysis and endovascular therapy for acute ischemic stroke with internal carotid artery occlusion: a systematic review of clinical outcomes. Stroke 2012;43(9):2362-8

62.

63.

64.

Benesˇ V 3rd, Buchvald P, Klimosˇova´ S, et al. Acute extracranial occlusion of the internal carotid artery: emergent surgery remains a viable option. Acta Neurochir (Wien) 2014;156(5):901-8.discussion 908-9 Weis-Mu¨ller BT, Huber R, Spivak-Dats A, et al. Symptomatic acute occlusion of the internal carotid artery: reappraisal of urgent vascular reconstruction based on current stroke imaging. J Vasc Surg 2008;47(4): 752-9.discussion 759 Weis-Mu¨ller BT, Spivak-Dats A, Turowski B, et al. Time is brain?–Surgical revascularization of acute symptomatic occlusion of the internal carotid artery up to one week. Ann Vasc Surg 2013;27(4): 424-32 Kasper GC, Wladis AR, Lohr JM, et al. Carotid thromboendarterectomy for recent total occlusion of the internal carotid artery. J Vasc Surg 2001;33(2):242-9.discussion 249-250 Randall M, Venables G, Beard J, Gaines P. Management of acute carotid occlusion. Eur J Vasc Endovasc Surg 2005;30(6):614-16



79.

Georgiadis D, Baumgartner RW. Thrombolysis in cervical artery dissection. Front Neurol Neurosci 2005;20:140-6

80.

Arnold M, Nedeltchev K, Sturzenegger M, et al. Thrombolysis in patients with acute stroke caused by cervical artery dissection: analysis of 9 patients and review of the literature. Arch Neurol 2002;59(4):549-53


81.

82.

83.

84.

85.

86.

87.

88.

89.

90.

Albers GW, Clark WM, Madden KP, Hamilton SA. ATLANTIS trial: results for patients treated within 3 hours of stroke onset. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. Stroke 2002;33(2):493-5 Clark WM, Wissman S, Albers GW, et al. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA 1999;282(21): 2019-26 Hacke W, Kaste M, Fieschi C, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995;274(13):1017-25 Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. N Engl J Med 1995;333(24):1581-7 Derex L, Nighoghossian N, Turjman F, et al. Intravenous tPA in acute ischemic stroke related to internal carotid artery dissection. Neurology 2000;54(11):2159-61 Georgiadis D, Lanczik O, Schwab S, et al. IV thrombolysis in patients with acute stroke due to spontaneous carotid dissection. Neurology 2005;64(9):1612-14 Rudolf J, Neveling M, Grond M, et al. Stroke following internal carotid artery occlusion - a contra-indication for intravenous thrombolysis? Eur J Neurol 1999;6(1):51-5 Engelter ST, Rutgers MP, Hatz F, et al. Intravenous thrombolysis in stroke attributable to cervical artery dissection. Stroke 2009;40(12):3772-6 Zinkstok SM, Vergouwen MDI, Engelter ST, et al. Safety and functional outcome of thrombolysis in dissection-related ischemic stroke: a meta-analysis of individual patient data. Stroke 2011;42(9):2515-20 Kremer C, Mosso M, Georgiadis D, et al. Carotid dissection with permanent and


transient occlusion or severe stenosis: long-term outcome. Neurology 2003;60(2): 271-5 91.

92.

93.

94.

95.

96.

97.

98.

Touze´ E, Randoux B, Meáry E, et al. Aneurysmal forms of cervical artery dissection: associated factors and outcome. Stroke 2001;32(2):418-23 Guillon B, Brunereau L, Biousse V, et al. Long-term follow-up of aneurysms developed during extracranial internal carotid artery dissection. Neurology 1999; 53(1):117-22 Georgiadis D, Caso V, Baumgartner RW. Acute therapy and prevention of stroke in spontaneous carotid dissection. Clin Exp Hypertens 28(3-4):365-70 Pham MH, Rahme RJ, Arnaout O, et al. Endovascular stenting of extracranial carotid and vertebral artery dissections: a systematic review of the literature. Neurosurgery 2011; 68(4):856-66.discussion 866 Goyal MS, Derdeyn CP. The diagnosis and management of supraaortic arterial dissections. Curr Opin Neurol 2009;22(1): 80-9 Kadkhodayan Y, Jeck DT, Moran CJ, et al. Angioplasty and stenting in carotid dissection with or without associated pseudoaneurysm. AJNR Am J Neuroradiol 2005;26(9):2328-35 Lavalleé PC, Mazighi M, Saint-Maurice J-P, et al. Stent-assisted endovascular thrombolysis versus intravenous thrombolysis in internal carotid artery dissection with tandem internal carotid and middle cerebral artery occlusion. Stroke 2007;38(8):2270-4 Kennedy F, Lanfranconi S, Hicks C, et al. Antiplatelets vs anticoagulation for dissection: CADISS nonrandomized arm and meta-analysis. Neurology 2012;79(7): 686-9

99.

Lyrer P, Engelter S. Antithrombotic drugs for carotid artery dissection. Cochrane Database Syst Rev 2010(10):CD000255

100.

Beletsky V, Nadareishvili Z, Lynch J, et al. Cervical arterial dissection: time for a therapeutic trial? Stroke 2003;34(12): 2856-60

101.

Touze´ E, Gauvrit J-Y, Moulin T, et al. Risk of stroke and recurrent dissection after a cervical artery dissection: a multicenter study. Neurology 2003;61(10):1347-51

102.

Mokri B, Piepgras DG, Sundt TM Jr, Pearson BW. Extracranial internal carotid artery aneurysms. Mayo Clin Proc 1982; 57(5):310-21

Review

103.

Peeters A, Goffette P, Dorban S, et al. An old dissecting aneurysm of the internal carotid artery presenting as acute stroke. Acta Neurol Belg 2003;103(3):179-82

104.

Arauz A, Hoyos L, Espinoza C, et al. Dissection of cervical arteries: long-term follow-up study of 130 consecutive cases. Cerebrovasc Dis 2006;22(2-3):150-4

105.

Morris-Stiff G, Teli M, Khan PY, et al. Internal carotid artery occlusion: its natural history including recanalization and subsequent neurological events. Vasc Endovascular Surg 2013;47(8):603-7

106.

Vicenzini E, Toscano M, Maestrini I, et al. Predictors and timing of recanalization in intracranial carotid artery and siphon dissection: an ultrasound follow-up study. Cerebrovasc Dis 2013;35(5):476-82

107.

Weimar C, Kraywinkel K, Hagemeister C, et al. Recurrent stroke after cervical artery dissection. J Neurol Neurosurg Psychiatry 2010;81(8):869-73

108.

Debette S, Metso T, Pezzini A, et al. Association of vascular risk factors with cervical artery dissection and ischemic stroke in young adults. Circulation 2011;123(14): 1537-44

109.

Dittrich R, Nassenstein I, Bachmann R, et al. Polyarterial clustered recurrence of cervical artery dissection seems to be the rule. Neurology 2007;69(2):180-6

110.

Schievink WI, Mokri B, O’Fallon WM. Recurrent spontaneous cervical-artery dissection. N Engl J Med 1994;330(6): 393-7

111.

Schievink WI, Mokri B, Piepgras DG, Kuiper JD. Recurrent spontaneous arterial dissections: risk in familial versus nonfamilial disease. Stroke 1996;27(4): 622-4

112.

Leys D, Bandu L, Heńon H, et al. Clinical outcome in 287 consecutive young adults (15 to 45 years) with ischemic stroke. Neurology 2002;59(1):26-33

113.

Dziewas R, Konrad C, Dra¨ger B, et al. Cervical artery dissection–clinical features, risk factors, therapy and outcome in 126 patients. J Neurol 2003;250(10): 1179-84

114.

De Bray JM, Marc G, Pautot V, et al. Fibromuscular dysplasia may herald symptomatic recurrence of cervical artery dissection. Cerebrovasc Dis 2007;23(5-6): 448-52

115.

Germain DP. Clinical and genetic features of vascular Ehlers-Danlos syndrome. Ann Vasc Surg 2002;16(3):391-7

doi: 10.1586/14737175.2014.955477

Review 116.

Nedeltchev K, Bickel S, Arnold M, et al. R2-recanalization of spontaneous carotid artery dissection. Stroke 2009;40(2):499-504

117.

Baracchini C, Tonello S, Meneghetti G, Ballotta E. Neurosonographic monitoring of 105 spontaneous cervical artery dissections: a prospective study. Neurology 2010;75(21): 1864-70

118.



119.

120.

Hosseini AA, Kandiyil N, Macsweeney ST, et al. Carotid plaque hemorrhage on magnetic resonance imaging strongly predicts recurrent ischemia and stroke. Ann Neurol 2013;73(6):774-84 Willats L, Connelly A, Christensen S, et al. The role of bolus delay and dispersion in predictor models for stroke. Stroke 2012; 43(4):1025-31 Gupta A, Chazen JL, Hartman M, et al. Cerebrovascular reserve and stroke risk in patients with carotid stenosis or occlusion: a systematic review and meta-analysis. Stroke 2012;43(11):2884-91

121.

Bryan DS, Carson J, Hall H, et al. Natural history of carotid artery occlusion. Ann Vasc Surg 2013;27(2):186-93

122.

Jokinen H, Schmidt R, Ropele S, et al. Diffusion changes predict cognitive and functional outcome: the LADIS study. Ann Neurol 2013;73(5):576-83

123.

Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke. Results of an international randomized trial. The EC/IC Bypass Study Group. N Engl J Med 1985;313(19):1191-200

124.

125.

126.

127.

128.

Grubb RL Jr, Powers WJ, Clarke WR, et al. Surgical results of the Carotid Occlusion Surgery Study. J Neurosurg 2013;118(1):25-33 Reynolds MR, Grubb RL Jr, Clarke WR, et al. Investigating the mechanisms of perioperative ischemic stroke in the Carotid Occlusion Surgery Study. J Neurosurg 2013;119(4):988-95 Amin-Hanjani S, Barker FG 2nd, Charbel FT, et al. Extracranial-intracranial bypass for stroke-is this the end of the line or a bump in the road? Neurosurgery 2012; 71(3):557-61 Ha¨nggi D, Steiger HJ, Vajkoczy P; Cerebrovascular Section of the European Association of Neurological Surgeons (EANS). EC-IC bypass for stroke: is there a future perspective? Acta Neurochir (Wien) 2012;154(10):1943-4 Grubb RL Jr, Derdeyn CP, Fritsch SM, et al. Importance of hemodynamic factors in the prognosis of symptomatic carotid occlusion. JAMA 1998;280(12):1055-60

doi: 10.1586/14737175.2014.955477

129.

130.

Powers WJ, Clarke WR, Grubb RL Jr, et al. Extracranial-intracranial bypass surgery for stroke prevention in hemodynamic cerebral ischemia: the Carotid Occlusion Surgery Study randomized trial. JAMA 2011;306(18):1983-92 Amarenco P, Benavente O, Goldstein LB, et al. Results of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial by stroke subtypes. Stroke 2009;40(4):1405-9

131.

Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med 2011;365(11):993-1003

132.

Ha¨nggi D, Steiger H-J, Vajkoczy P. The Role of MCA-STA Bypass Surgery After COSS and JET: the European Point of View. Acta Neurochir Suppl 2014;119:77-8

133.

Antithrombotic Trialists’ Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324(7329): 71-86

134.

A comparison of two doses of aspirin (30 mg vs. 283 mg a day) in patients after a transient ischemic attack or minor ischemic stroke. The Dutch TIA Trial Study Group. N Engl J Med 1991;325(18):1261-6

135.

Diener HC, Cunha L, Forbes C, et al. European Stroke Prevention Study. 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke. J Neurol Sci 1996;143(1-2):1-13

136.

ESPRIT Study Group. Halkes PH, van Gijn J, Kappelle LJ, et al. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet 2006;367(9523):1665-73

137.

Halkes PH, Gray LJ, Bath PM, et al. Dipyridamole plus aspirin versus aspirin alone in secondary prevention after TIA or stroke: a meta-analysis by risk. J Neurol Neurosurg Psychiatry 2008;79(11):1218-23

138.

Leonardi-Bee J, Bath PM, Bousser MG, et al. Dipyridamole for preventing recurrent ischemic stroke and other vascular events: a meta-analysis of individual patient data from randomized controlled trials. Stroke 2005;36(1):162-8

139.

Sacco RL, Diener HC, Yusuf S, et al. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. N Engl J Med 2008;359(12):1238-51

140.

Uchiyama S, Ikeda Y, Urano Y, et al. The Japanese aggrenox (extended-release dipyridamole plus aspirin) stroke prevention

versus aspirin programme (JASAP) study: a randomized, double-blind, controlled trial. Cerebrovasc Dis 2011;31(6):601-13 141.

CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 1996;348(9038): 1329-39

142.

S3-Leitlinie zur Diagnostik, Therapie und Nachsorge der extracraniellen Carotisstenose, AWMF-Registernummer 004–028. Available from: www.awmf.org [Last accessed on 25 May 2013]

143.

Eckstein HH, Ku¨hnl A, Do¨rfler A, et al. The diagnosis, treatment and follow-up of extracranial carotid stenosis: a multidisciplinary German-Austrian guideline based on evidence and consensus. Dtsch A¨rztebl Int 2013;110(27-28):468-76

144.

Brott TG, Halperin JL, Abbara S, et al. 2011 ASA/ACCF/AHA/AANN/AANS/ ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/ SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery. J Am Coll Cardiol 2011;57(8): 1002-44

145.

Goldstein LB, Bushnell CD, Adams RJ, et al. Guidelines for the primary prevention of stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42(2):517-84

146.

European Stroke Organisation. Tendera M, Aboyans V, et al. ESC Guidelines on the diagnosis and treatment of peripheral artery diseases: Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries: the Task Force on the Diagnosis and Treatment of Peripheral Artery Diseases of the European Society of Cardiology (ESC). Eur Heart J 2011;32(22):2851-906




147.

Ricotta JJ, Aburahma A, Ascher E, et al. Updated Society for Vascular Surgery guidelines for management of extracranial carotid disease. J Vasc Surg 2011;54(3): e1-31

148.

Furie KL, Kasner SE, Adams RJ, et al. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011;42(1):227-76

149.

Liapis CD, Bell PR, Mikhailidis D, et al. ESVS guidelines. Invasive treatment for carotid stenosis: indications, techniques. Eur J Vasc Endovasc Surg 2009;37(4 Suppl): 1-19


150.

Markus HS, Droste DW, Kaps M, et al. Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using Doppler embolic signal detection: the Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial. Circulation 2005;111(17):2233-40

151.

Wang Y, Wang Y, Zhao X, et al. Clopidogrel with aspirin in acute minor stroke or transient ischemic attack. N Engl J Med 2013;369(1):11-19

152.

Bhatt DL, Fox KA, Hacke W, et al. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 2006;354(16): 1706-17

Review

153.

Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet 2004;364(9431):331-7

154.

Seitz RJ, Siebler M. Platelet GPIIb/IIIa receptor antagonists in human ischemic brain disease. Curr Vasc Pharmacol 2008; 6(1):29-36

155.

Siebler M, Hennerici MG, Schneider D, et al. Safety of Tirofiban in acute Ischemic Stroke: the SaTIS trial. Stroke 2011;42(9): 2388-92

doi: 10.1586/14737175.2014.955477

Surgical treatment for pseudo-occlusion of the internal carotid artery.

Bilateral atherosclerotic internal carotid artery occlusion and recurrent ischaemic stroke.

Blood pressure variability and stroke outcome in patients with internal carotid artery occlusion.

Pseudo-occlusion of the internal carotid artery.

Intra-arterial treatment of patients with acute ischemic stroke and internal carotid artery occlusion: a literature review.

Permanent oculomotor palsy with occlusion of the internal carotid artery.

Traumatic internal carotid artery occlusion--case report.

Treatment options for asymptomatic carotid artery stenosis.

Emergency carotid artery stenting in patients with acute ischemic stroke due to occlusion or stenosis of the proximal internal carotid artery: a single-center experience.

Recanalization therapy for internal carotid artery occlusion presenting as acute ischemic stroke.

Emergent cervical surgical embolectomy for extracranial internal carotid artery occlusion.

Increased high-sensitivity C-reactive protein, erythrocyte sedimentation rate and lactic acid in stroke patients with internal carotid artery occlusion.

Prognosis of patients with unilateral extracranial occlusion of the internal carotid artery.

Neurocognitive improvement after carotid artery stenting in patients with chronic internal carotid artery occlusion: a prospective, controlled, single-center study.

Unilateral Internal Carotid Artery Occlusion After Letrozole Treatment in a Postmenopausal Woman with Breast Cancer.

Natural history of acute stroke due to occlusion of the middle cerebral artery and intracranial internal carotid artery.

External carotid artery in internal carotid artery occlusion. Angiographic, therapeutic, and prognostic considerations.

Distribution of internal carotid artery plaque locations among patients with central retinal artery occlusion in the Eagle study population.

Late spontaneous recanalization of symptomatic atheromatous internal carotid artery occlusion.

Two cases of spontaneous internal carotid artery occlusion due to giant intracranial carotid artery aneurysm.

Clinical and imaging features associated with intracranial internal carotid artery calcifications in patients with ischemic stroke.

Internal carotid artery occlusion should not exclude surgery.

Internal carotid artery occlusion caused by giant cell arteritis.

Pituitary apoplexy producing internal carotid artery occlusion. Case report.