Intracranial Atherosclerotic Disease: Diagnosis, and Medical and Endovascular Management

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Intracranial atherosclerotic disease accounts for 8% of all strokes.81,82 Intracranial atherosclerotic disease is increasingly being discovered with the liberal use of intracranial MR and CT angiography. Both symptomatic and asymptomatic patients are being evaluated more frequently with these noninvasive techniques. The treatment of these lesions has been principally with either antiplatelet (aspirin) or anticoagulant (sodium warfarin) medications. Randomized trials are underway to determine whether aspirin or warfarin is more effective for the treatment of symptomatic intracranial atherosclerotic lesions.83,84 Because of the dismal prognosis associated with intracranial atherosclerosis despite medical treatment, alternative treatment options are being explored. Interventional techniques have revolutionized the treatment of coronary atherosclerotic disease and are similarly leading to significant improvements in the treatment of peripheral atherosclerotic disease. Technological advancements in angioplasty catheters and stents have driven the application of these devices for revascularization of the intracranial circulation. To date, only small patient series have been reported in the literature.

This section includes a review of the current literature concerning the natural history of intracranial atherosclerotic disease and different endoluminal revascularization strategies for the treatment of symptomatic intracranial atherosclerotic lesions. Using this information, laboratory evidence, and our experience, we discuss our revascularization management strategies, including the use of staged stenting procedures. Finally, complication avoidance and management are mentioned.


The management of intracranial atherosclerosis remains perplexing. Unlike for atherosclerosis of the extracranial vasculature, only one prospective randomized trial has influenced therapeutic approaches for intracranial disease. The Extracranial-to-Intracranial (EC-IC) Cooperative Bypass Study demonstrated the inefficacy of bypass surgery to prevent stroke recurrence.85 This study and other smaller prospective studies have allowed us to define the natural history of intracranial arterial stenosis. In all of these studies, patients were enrolled after the occurrence of a defining neurologic event (transient ischemic attack {TIA} or stroke) referable to the vascular distribution of the intracranial stenotic vessel.

There are several studies, including the EC-IC bypass study, in which a subgroup of patients was treated with aspirin alone. In the bypass study, 714 patients with intracranial ICA or MCA stenosis who received aspirin (1300 mg daily) were observed. The annual stroke rate referable to the stenosis was 7%, with an overall stroke rate of 10%. Craig et al. followed up 58 patients for 2.5 years and discovered a 43% stroke rate and a 15% mortality rate.86 Marzewski et al. followed up 66 patients with distal ICA stenosis and noted a 3.2% annual stroke rate ipsilateral to the stenosis, with a mortality of 46% over 44 months.87 Ischemic cerebrovascular disease was responsible for the death of 27% of these patients.

The retrospective arm of the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) study examined the efficacy of warfarin compared to aspirin for the prevention of major vascular events (stroke, MI, or sudden death).83 Among 63 patients treated with aspirin, the rate of stroke was 10.4 per 100 patient years, which corroborates well with the rates reported in other studies. Among patients receiving warfarin, however, the stroke rate decreased to 3.6 per 100 patient years. Three patients had major hemorrhagic complications, with two being fatal. The rate of hemorrhagic complications for the warfarin-treatment group was 7.8 per 100 patient years, compared with 1.4 per 100 patient years for the aspirin-treatment group.83 In summary, the risk of stroke or hemorrhagic event for patients receiving warfarin was 11.4 per 100 patient years, whereas the rate of stroke or hemorrhagic event for those receiving aspirin was 11.8 per 100 patient years. Adding to the complexity of medication choices, a trial conducted more recently in Europe, the Stroke Prevention in Reversible Ischemia Trial (SPIRIT), demonstrated a high hemorrhagic complication rate associated with warfarin therapy in patients who experienced previous cerebral ischemic events.88 Moreover, in the Warfarin versus Aspirin in the Secondary Prevention of Stroke Study (WARSS), a randomized controlled study of 2206 patients comparing low-dose anticoagulation (international normalized ratio 1.4 to 2.8) versus aspirin (325 mg daily) for patients with a non-cardiogenic source of stroke, warfarin was not proven to be more effective than aspirin in preventing stroke recurrence.

In the WASID trial, the occurrence of strokes in vascular territories outside the significant stenosis were nearly eliminated as a result of warfarin therapy.83 Among six patients who had strokes, five strokes were in the territory of the compromised vessel. With aspirin, 15 strokes occurred, of which nine were in the territory of the stenotic artery. Warfarin therapy likely reduces the incidence of stroke outside the territory of the stenotic vessel by reducing the cardioembolic risk of stroke and has been repeatedly shown to significantly reduce the risk of stroke in patients with atrial fibrillation.89-91 Increasingly, strokes are thought to be caused by a variety of potential cardiac sources in patients without previously identifiable etiologies. Warfarin, therefore, is likely effective for the prevention of concomitant sources of stroke in the population with potential cardiac thromboembolic sources with concomitant intracranial atherosclerosis, resulting in the lower stroke rate in these patients than in those treated with aspirin alone.

For patients who experience neurological symptoms despite antithrombotic treatment, the risk of recurrent events is very high (47.7% over a mean follow-up period of 14.7 months, with a median time to recurrence of 32 days).There is, therefore, some urgency to change the form of treatment once failure has occurred. In addition, most patients with intracranial disease are more likely to present with a major event (such as a catastrophic stroke) than with a TIA or a minor stroke.85 This risk of a stroke with potentially irreversible neurological deficits further complicates medical decision-making as the question arises whether medical management should even be attempted initially.


Intracranial stenosis is a dynamic process whereby repeat angiographic imaging can sometimes reveal dramatically different degrees of arterial blockage. Akins et al. presented a retrospective series of serial angiographic studies obtained to study the dynamic morphology of asymptomatic intracranial stenosis.93 In this series of 21 patients with 45 intracranial stenotic lesions, 40% of the lesions progressed and 20% regressed over a 7-year period. The distal ICA did not seem as predisposed to disease progression as did the more distal branches (MCA, anterior cerebral artery, posterior cerebral artery). In three patients, regression of the intracranial stenosis was impressive, suggesting that a thrombus was present within the already diseased vessel. In addition, 23% of the patients in this series had strokes during the follow-up period while receiving different antithrombotic regimens.

More recently, significant angiographic improvement of a stenotic vertebrobasilar artery segment was seen after the administration of high-dose atorvastatin, a potent HMG-CoA reductase inhibitor, for a 2-week period.94 This improvement may have been from resolution of thrombus because statins promote endogenous fibrinolysis and plaque remodeling.


There is considerable debate about the mechanism responsible for large vessel stenosis that leads to stroke. Unlike the extracranial carotid where artery-to-artery embolism is the predominant mechanism, increasing evidence in the literature supports a hemodynamic cause for large vessel infarctions. Certainly, a subset of patients has demonstrated a higher rate of stroke recurrence associated with hemodynamic failure.95-97 More likely, there is an ongoing interaction between the stenosis providing an embolic source and reduced blood flow resulting in diminished ability to clear the emboli. The ischemic events are thus a shift in the balance between embolic load and blood flow.98 As warfarin is an effective anticoagulant, the number of emboli generated by an intracranial stenosis may be reduced with its use. Despite warfarin therapy, a significant number of infarctions occurred in the territory of the stenotic vessel in the WARSS and WASID studies.83,84 This phenomena reinforces the supposition that diminished blood flow is the cause for numerous infarctions related to intracranial atherosclerosis. Warfarin is highly effective in treating cardioembolic sources of stroke when adequate blood flow is present.

Unlike warfarin, bypass surgery can augment cerebral blood flow and reduce hemodynamic risk of future strokes, but it has little ability to reduce artery-to-artery embolism. The EC-IC bypass study failed to demonstrate a reduction in stroke frequency, partly because the patient population could not be selected to a hemodynamic failure arm.85 Technology such as positron emission tomography (PET), single-photon emission CT (SPECT), or Xenon-enhanced CT was unavailable during the study period. Thus, TIAs or strokes resulting from emboli versus ischemia were difficult to differentiate between. In addition, the EC-IC bypass procedure occasionally precipitates MCA occlusion at the site of the stenotic segment (usually the M1 segment).99,100 This thrombosis likely causes perforator occlusion, resulting in deep brain infarction.

In summary, aspirin has demonstrated only mild efficacy for stroke prevention. Warfarin may prove to be more efficacious, yet it poses a significant stroke risk attendant to the threatened territory and a possible increased threat of hemorrhagic complication. Endoluminal revascularization, therefore, may have a role in the treatment of both embolic and hemodynamic sources of infarction from the stenotic vessel.


The methods for achievement of endoluminal revascularization are primary angioplasty, primary stenting, direct stenting (stenting without immediate balloon predilation). and provisional stenting. Primary angioplasty means that the operator places an angioplasty balloon to expand the stenotic segment and has no intention of placing a stent. Primary stenting means that the operator has the intention of placing a stent and may or may not dilate the lesion with an angioplasty balloon before stent placement. If no previous dilation is required, the procedure is referred to as direct stenting. Provisional stenting refers to stent-placement following unsatisfactory luminal recanalization from angioplasty, or stenting as a “bail-out” procedure.

The feasibility and limitations of primary angioplasty were presented in initial patient series.101-104 The periprocedural risk of stroke or death was 8 to 33%. More recent series have documented the decreased incidence of complications, demonstrating a considerable learning curve for these techniques.105-108 The periprocedural neurological event rate in these series, which comprised more than 10 patients each, was less than 10%.

The results of these numerous reports are mirrored in the angioplasty series presented by Connors and Wojak.105 These authors divided their experience from 1989 to 1998 into three periods. A higher rate of complications was encountered in 17 patients treated during the early and middle periods from 1989 to 1993 including dissection in 82%, neurological events in 6%, and death in 6%. Subsequent to 1993, the rates among 41 patients were dissection in 14%, neurological events in 8% (of which 4% were TIAs), and death in 2%. Connors and Wojak attribute the improvements to decreasing the balloon diameter to restore the vessel lumen, very slow inflation of the balloon (over 2-5 minutes), and the routine use of glycoprotein IIb/IIIa receptor inhibitors, such as abciximab, during angioplasty. Two hemorrhages (included in the neurological events rate) occurred during this period. They also avoid crossing a lesion more than once with the angioplasty balloon because that maneuver is likely to raise an intimal flap and cause the vessel to become occluded. One intrinsic advantage of endovascular approaches over surgery is the ability to repeat the angioplasty. A stenotic vessel that has been suboptimally dilated initially can be further dilated on subsequent interventions. Another “pearl” discovered by Connors and Wojak is the use of shorter angioplasty balloons to prevent straightening of the intracranial vessels after balloon inflation, making injury or dissection less likely.

In a single series of clinically symptomatic patients with hemodynamically significant intracranial lesions, Mori et al. demonstrated the effectiveness of angioplasty in patients with short (≤5 mm), mildly eccentric or concentric (type A) lesions.107 In their experience, angioplasty of these lesions resulted in a periprocedural complication rate of 8% (1 stroke in 12). During the 2-year follow-up period, no ipsilateral stroke, neurological event, or angiographic stenosis occurred; and no bypass surgery or repeat angioplasty was needed. For angiographic lesions that were longer and more eccentric or chronically occluded, the procedure yielded less effective results. For lesions that were either 5 to 10 mm in length or totally occluded and were less than 3 months old (type B), the success rate was 86%. Angiographic restenosis occurred in 33% of lesions within the 2-year follow-up period. Angioplasty attempts were unsuccessful in 2 of 21 patients. Patients with chronically occluded lesions that were 3 months or older or highly angular or long (>10 mm in length) (type C) fared the worst. Angioplasty was associated with an initial success rate of 33% (3 of 9 patients) and a restenosis rate of 100% at 1 year. These results suggest that angiographic characteristics may help determine feasibility and periprocedural risks. One of 9 patients with type C lesions experienced a stroke from abrupt closure of the stenotic vessel, suggesting that vessels harboring these lesions are extremely tenuous.107 The cumulative risk of ipsilateral stroke was 12% for type B lesions and 56% for type C lesions. Of note, the natural history of these lesions was not delineated according to lesion type in either the WASID study or the EC-IC bypass study. Reports by Mori et al.109,110 suggest that type C and possibly type B lesions as well should not be treated by angioplasty alone but rather may benefit from another endovascular technique or surgery.

Marks et al. reported a low periprocedural risk of 5% in their intracranial angioplasty series. Like Connors and Wojak,105 they undersized the balloon and allowed for residual stenosis. They frequently included anticoagulation (warfarin) therapy in their postprocedural regimen (prescribed for 18 of 23 patients), particularly if there was significant (>50%) residual stenosis or dissection. Two complications occurred in the immediate postprocedural period among this group of 23 patients. A vessel ruptured, which resulted in death; and an angioplasty site became occluded by a thrombus. The clot was successfully lysed with IA tissue plasminogen activator. Two strokes occurred during the respective follow-up periods of 37 and 32 months. Only one of the strokes involved territory supplied by the treated vessel. This stroke occurred in a vessel with 50% residual stenosis. Including the vessel rupture, the annual rate of stroke in the territory of the previously treated vessel was 3.2%, and the overall rate of stroke during the average 35.4 months of follow-up was 4.8%. This dramatically low frequency of strokes should be acknowledged because it occurred while warfarin therapy was often used in conjunction with revascularization therapy. This combination of therapies may best reduce the risk of strokes from hemodynamic, embolic, and small vessel arteriopathy sources.

In summary, primary angioplasty provides an effective method of endoluminal revascularization. The intrinsic disadvantages of angioplasty are mirrored in the coronary literature.111-113 Coronary angioplasty alone resulted in numerous dissections or vessel recoil that would have been resolved with stent placement. Moreover, there was a low incidence of mortality related to vessel rupture during balloon inflation or hemorrhage associated with reperfusion and use of IIb/IIIa inhibitors. Strokes were rare, but ischemic neurological events occurred either periprocedurally or immediately after angioplasty. The incidence of neurological events was probably higher in Mori type C lesions. The vessels at greatest risk for restenosis or further strokes were those with residual stenosis, yet the vessels at greatest risk of rupture or dissection were those inflated with a balloon that was the size of the vessel or larger. In follow-up of angioplasty performed for intracranial atherosclerosis, the results appear durable if minimal residual stenosis is apparent. In almost all series reporting delayed neurological events, these events occurred among patients with residual vessel stenosis seen immediately after completion of the procedure.

The limitations of primary angioplasty prompted investigators to examine the effectiveness of primary stent placement for the treatment of intracranial atherosclerosis. There are three series including at least 10 patients each who underwent intracranial primary stenting for atherosclerotic lesions.114-116 The first two series report excellent results, with minimal residual stenosis and no neurological complications.114,116 Mori et al. were unable to deliver a stent in two of 12 lesions but were able to successfully perform angioplasty of these lesions.116 Improvements in trackability and flexibility will make stents easier to deliver. In the series reported by Mori et al., two lesions were type C and eight lesions were type B lesions.116 One type C lesion could not be accessed for stent delivery, which again demonstrates the difficulty in treating this kind of lesion. No restenosis or neurological events have been reported in the early postprocedural (<4 months) period. Type B lesions might be best treated with stent placement. Gomez et al. successfully placed stents in the basilar or intracranial vertebral arteries in 12 patients.114 No technical failures or ischemic neurological events occurred in this series. Three of 12 patients had headaches and two had cranial nerve deficits, all of which resolved within 3 months. The cranial nerve deficits were likely related to nerve injury resulting from basilar artery manipulation during stent placement.

In the third series reported, Levy et al. presented a series of 11 patients with medically refractory vertebrobasilar insufficiency.115 Primary intracranial stent placement was performed in each case. Technical success was achieved in nine of 11 patients (82%); four periprocedural complications occurred that resulted in death (mortality rate 36%). In two of the remaining seven patients, intimal hyperplasia developed within or at the end of the stent, and the formation of a pseudoaneurysm was seen at the end of one stent. This series reflects several important findings. Despite routine use of abciximab and heparin, a significant incidence (29%, 2 of 7 surviving patients) of thromboembolic complications was associated with stent placement in the basilar artery. Levy et al. mention that balloon angioplasty was occasionally performed before stent placement was performed, which indicates that most patients in this series were treated with direct stent placement. In addition, intraprocedural rupture was the cause of death in two of the four patients who died. Vessel rupture occurred in or around the vertebrobasilar junction where hypoplastic vessels may arise. Because of this anatomical variability, obtaining measurements to select a stent of an appropriate diameter is particularly difficult. In the first two series reported by Gomez et al. and Mori et al., the stenotic lesions were predilated with an angioplasty balloon before stent placement (primary stent procedure).114,116 More recently, Ramee et al. have proposed a combined approach for the treatment of symptomatic intracranial stenosis.117 They used primary angioplasty for revascularization of lesions classified as Mori type A. If the lesion was complex or long, primary stenting was attempted. If the results of primary angioplasty were suboptimal because of dissection or vessel recoil with residual stenosis, a stent was placed. The combined approach yielded an excellent short-term outcome with a 93% success rate and a 53% “unexpected benefit” rate in that 8 of 15 patients had reversal of what was initially thought to be a permanent deficit from a previous stroke. Ten of the 15 patients in this series underwent angioplasty alone. Primary stenting was attempted in four patients in whom the lesions were complex and long. Stent placement was unsuccessful in one of these patients, who then underwent angioplasty alone, which resulted in 30% residual stenosis. Severe elastic recoil encountered during angioplasty of petrous carotid stenosis in two patients necessitated stent deployment to achieve a better initial result (provisional stent placement). This method is described in the coronary literature as provisional stenting and has become popular for coronary revascularization.

Our revascularization management strategies have reflected those depicted in the literature. We used angioplasty alone in our early revascularization experience. We developed techniques similar to those of Connors and Wojak105 in that we typically undersize the vessel and use slow inflation and deflation techniques. One significant difference between our technique and theirs is that we use less compliant coronary balloons that are precisely sized to the vessel for angioplasty procedures. Precise measurements of the stenotic segment and the adjacent parent artery lumen are important to prevent the risk of vessel dissection or rupture as a result of inadvertent oversizing of the angioplasty balloon. One potential disadvantage associated with the use of less compliant balloons is that the material used to construct the balloon has a higher durometry (i.e., amount of force needed to expand the balloon and, in turn, the amount of force exerted on the parent vessel). As such, more force is required to advance this type of balloon through tortuous vessels. These balloons may be more difficult to navigate into intracranial vessels than more compliant balloons. To facilitate balloon delivery, the shortest balloon length that covers the lesion should be chosen. For short lesions, a 10-mm length balloon would be used. For longer lesions, a 15- or 20-mm balloon can be used. Longer balloons may be more difficult to deliver and may require distal wire purchase. Inflations are kept below 8 atm, and the balloon is slowly inflated and deflated. We typically use coronary exchange length wires that allow us to exchange devices without re-crossing the lesion with the wire. Therefore, a suboptimal angioplasty result (because of dissection, vessel recoil, or thrombus) can be treated with either stent placement or repeat angioplasty with a balloon of a different size.

Anatomically, there are several reasons for different responses of intracranial and coronary vessels to endoluminal revascularization. The high incidence of vessel dissection, rupture, and recoil encountered during intracranial revascularization procedures can be explained by these anatomical differences. The histology and physiology of the intracranial vessels change as these vessels course through the skull base. Once within the skull, they become conduit vessels within a fixed space (the skull) with a constant volume occupied by the brain, cerebrospinal fluid, and blood. These histological and pathological changes result in thin-walled subarachnoid vessels that transport a large volume of circulating fluid. Cross-sectional histology of intracranial vessels demonstrates a loss of the vasa vasorum and external elastic membranes. Near absence of the adventitia is noted. The tunica media is composed of principally smooth muscle cells.118 Such modified vessels are more likely to rupture or dissect during endoluminal revascularization procedures. Moreover, a more robust smooth muscle cell response to angioplasty or stent placement is likely to occur in these vessels, resulting in intimal hyperplasia.

Because of these anatomical differences and initial results of balloon angioplasty demonstrating a higher incidence of dissection (85%, Connors and Wojak105) and rupture (5-10%, Marks et al106 and Connors and Wojak105) in the intracranial vasculature when using coronary techniques (i.e., angioplasty balloons are sized 10 to 20% larger than the reference vessel, and quick inflation and deflation are preferred), alternative methods of revascularization were sought. The authors use balloons that are clearly smaller in diameter than the parent vessel. For instance, a 1.5 or 2.0-mm balloon will be used in the MCA or BA. We are increasingly allowing for residual stenosis at the time of the initial intervention. If residual stenosis exists but is not flow limiting (<50%), a staged stent procedure is planned in which stent placement is performed 6 to 8 weeks after angioplasty. We use this technique because periprocedural risks such as dissection and rupture are minimized by use of a small diameter balloon during the initial angioplasty procedure. Residual stenosis portends a higher risk of subsequent symptomatic restenosis or a thromboembolic event; however, in the angioplasty series with the longest follow-up reported in the current literature,106 most of these thromboembolic events occurred after 6 months (indeed two strokes occurred at 32 and 37 months after treatment). Therefore, leaving a residual stenosis for 6 to 8 weeks to allow for an intimal response is unlikely to incur a significant neurological risk. This strategy is particularly useful for complex, long, or recently symptomatic stenoses where the risk of periprocedural neurological complications is highest.119 By performing a simple undersized balloon angioplasty first, plaque fracture and injury are less likely to occur. Intimal response that occurs over the ensuing weeks may make subsequent stent placement safer, thereby reducing the chance of dissection, distal embolization, or snowplowing (closure of perforating side branches by plaque as the stent or balloon is deployed as a result of plaque fracture and compression). At our institution, direct stent placement is believed to increase the chances of snowplowing and is therefore no longer used unless the stenosis is in a region without eloquent perforating vessels. Data is needed to corroborate this hypothesis. We no longer use IIb/IIIa inhibitors routinely for intracranial angioplasty and stent placement because of the associated risk of hemorrhage. Connors and Wojak presented two hemorrhages in a series of 41 patients.105 We use abciximab or eptifibatide as a bail-out treatment alternative when thromboembolic complications occur.

Initially, the use of intracranial stents was reserved for cases in which significant vessel recoil or dissection lead to the failure of a previous angioplasty procedure. With greater experience, we are learning that certain sites are more likely to respond better to stent placement than angioplasty alone. For instance, angioplasty of a petrous carotid stenosis usually results in significant vessel recoil, so stent placement is necessary.117,120 This area is also proximal in the vessel tree, allowing for more consistent ability to place the stent. Stent delivery, placement, and deployment involve a steep learning curve. Our experience with intracranial stents was preceded by a robust animal experience. We would suggest that these techniques be practiced in models before they are applied clinically. As mentioned previously, the decision to perform stent placement should be made on the basis of post-angioplasty results. Excessive vessel recoil or dissection may mandate stent placement. The stent diameter should be equal to the nominal vessel diameter. The stent length should be chosen so that the entire lesion will be covered with an additional 1 to 2-mm overlap onto the healthy vessel on each side. Minimizing the length of the stent is important for navigation of the proximal tortuosity of the skull base. It also may decrease the incidence of intimal hyperplasia.

Stent Delivery

Stent delivery can be difficult, especially when the radius of curvature of the carotid siphon or VA near the C1 vertebra is low. It is critical that the guide wire has a firm purchase in the distal vessel. For a stent to be positioned in the supraclinoid carotid artery, the wire should be positioned in the M2 or M3 segment of the ipsilateral MCA. For a midbasilar stenosis, the wire should be positioned in the P2 or P3 segment of the posterior cerebral artery. During delivery, the position of the distal end of the guide catheter should be carefully monitored. As the stent is negotiated through tight turns in the vasculature, the guide catheter may back out. This movement can result in loss of guide catheter position and distal wire purchase. Extreme caution must be taken to advance the guide catheter distally to ensure adequate support for stent delivery. On occasion, a second wire (V18 Control, Boston Scientific Scimed, Maple Grove, MN) is placed in the guide catheter for improved stability. More recently, guide catheters are supported by guide sheaths of appropriate length that allow selection of the great vessels arising from the aortic arch. For instance, a Cook shuttle or armored arrow sheath (Cook Inc., Bloomington, IN) is placed 10 to 20 cm proximal to the guide catheter. The guide sheath provides the guide catheter with considerable stability, allowing the angioplasty catheter or stent to be advanced through tortuous anatomy.

Once the stent has been advanced across the lesion, careful attention must be paid to positioning. Before deploying the stent, we routinely perform numerous digital subtraction angiographic studies to ensure that the lesion is adequately covered by the stent. Rarely will patients become symptomatic as a result of flow obstruction caused by the stent before deployment. It is advisable to ensure that the stent is positioned properly before deployment. Deployment should be performed slowly and evenly. The balloon should be expanded fully, and the stent should be imbedded into normal vessel proximal and distal to the lesion. Digital subtraction angiography is performed after the procedure to confirm placement, patency, and apposition of the stent to the vessel wall. If post-stent angioplasty is necessary, it can be performed with a slightly larger balloon. If the stent does not adequately cover the lesion, another stent should be placed. Sluggish flow or evidence of thrombus within the stent may require the administration of IIb/IIIa inhibitors to prevent acute or subacute thrombosis. Angiography of the distal vasculature must be carefully examined to ensure that distal embolization has not occurred.

At the conclusion of the procedure, the effect of the heparin is allowed to reverse on its own. The sheath can be left in place and removed when the coagulation cascade has normalized within 4 to 6 hours, after which pressure can be applied to the groin region to ensure hemostasis. Alternatively, a femoral artery closure device can be used at the conclusion of the procedure. During the perioprocedural period, blood pressure is closely monitored and controlled. Clopidogrel, which was administered for the 3 days leading up to the procedure, is continued for 30 days. Aspirin is prescribed for the life of the patient. The authors advocate the use of stents for failed angioplasty. We have begun to also use stent placement routinely in certain sites, such as the petrous carotid artery, and for certain types of lesions. Mori type C and B lesions have a high incidence of restenosis and subsequent neurological events. For these, we use the aforementioned staged procedure. The initial undersized angioplasty improves cerebral blood flow through the vessel significantly. Then, an intimal response occurs. Six to 8 weeks after the angioplasty, stent placement is performed if significant stenosis remains. In this delayed fashion, the stent procedure may not carry the same thromboembolic risk but does afford the advantage of better acute gain (the vessel is opened wider than with angioplasty alone) and a resultant decrease in symptomatic restenosis. On occasion, staged stent placement is not required because the vessel undergoes positive remodeling and the luminal angiographic diameter of the blood vessel improves as a result of the angioplasty alone.


The natural history of intracranial atherosclerosis must be well understood to optimize patient selection for and timing of endoluminal revascularization. Our techniques have evolved such that we perform revascularization in symptomatic patients after angiographic documentation of high-grade intracranial stenosis and blood-flow assessment revealing hypoperfusion in the threatened territory or symptoms related to the stenosis. We are increasingly using stent-assisted angioplasty for complex plaques or when initial angioplasty results are suboptimal. Our current stent of choice is the Wingspan stent from Boston Scientific, as it has an HDE approval for intracranial stenosis. Additionally, it is more flexible than balloon mounted stents (as it is a self-expanding stent). Despite early European results of 10%, large series by the Wingspan Users Group (Cleveland Clinic, University at Buffalo, UT Southwestern, University of Wisconsin) have demonstrated a 30% rate of restenosis. Additionally, approximately 10% had symptom recurrence.

The decision to perform revascularization becomes more difficult when hypoperfusion on SPECT, PET, or Xenon-enhanced CT imaging is not demonstrated or the patient has not failed a course of treatment with antiplatelet agents. This group of patients could either be enrolled in the WASID trial to receive maximal medical therapy or could undergo endoluminal revascularization. Another challenging group includes asymptomatic patients with MR angiography evidence of intracranial stenosis. We do not consider these patients for endoluminal revascularization unless radiologic studies reveal moderate or severe hypoperfusion or lack of reserve in a patient who is to undergo a coronary bypass procedure.

The authors’ techniques for endoluminal revascularization of intracranial stenosis have evolved in accordance with the literature. We use short, undersized angioplasty balloons with slower inflations. Two different antiplatelet agents (clopidogrel and aspirin) are administered for 72 hours before the procedure; IIb/IIIa inhibitors may be administered during revascularization of longer, ulcerated lesions. Stent-assistance is used as a rescue tactic for dissection or occlusion subsequent to angioplasty. A staged stent procedure is used for complex or difficult stenoses, particularly those in regions of eloquent perforators.119

Ongoing advancements in microcatheters, microwires, angioplasty balloons, and intravascular stents have enhanced our ability to successfully treat intracranial atherosclerotic lesions. A role for endoluminal revascularization of these lesions is apparent, particularly for those with concentric, short stenoses. Models for intracranial atherosclerosis and endovascular treatments of these stenoses are necessary to gain insight into the vascular responses following endoluminal device placement. Moreover, the potential use of pharmacologically enhanced stent-coatings must be tested with the intracranial vasculature, as these devices may significantly impact the long-term effectiveness of stenting for atherosclerotic disease.


  1. Wityk RJ, Lehman D, Klag M, Coresh J, Ahn H, Litt B. Race and sex differences in the distribution of cerebral atherosclerosis. Stroke. 1996;27:1974-1980.
  2. Chimowitz MI, Kokkinos J, Strong J, Brown MB, Levine SR, Silliman S, Pessin MS, Weichel E, Sila CA, Furlan AJ, et al. The Warfarin-Aspirin Symptomatic Intracranial Disease Study. Neurology. 1995;45:1488-1493.
  3. Redman AR, Allen LC. Warfarin Versus Aspirin in the Secondary Prevention of Stroke: The WARSS Study. Curr Atheroscler Rep. 2002;4:319-325.
  4. The EC-IC bypass study. N Engl J Med. 1987;317:1030-1032.
  5. Craig DR, Meguro K, Watridge C, Robertson JT, Barnett HJ, Fox AJ. Intracranial internal carotid artery stenosis. Stroke. 1982;13:825-828.
  6. Marzewski DJ, Furlan AJ, St Louis P, Little JR, Modic MT, Williams G. Intracranial internal carotid artery stenosis: longterm prognosis. Stroke. 1982;13:821-824.
  7. Gorter JW. Major bleeding during anticoagulation after cerebral ischemia: patterns and risk factors. Stroke Prevention In Reversible Ischemia Trial (SPIRIT). European Atrial Fibrillation Trial (EAFT) study groups. Neurology. 1999;53:1319-1327.
  8. Stroke Prevention in Atrial Fibrillation Study. Final results. Circulation. 1991;84:527-539.
  9. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med. 1994;154:1449-1457.
  10. Petersen P, Boysen G, Godtfredsen J, Andersen ED, Andersen B. Placebo-controlled, randomised trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation. The Copenhagen AFASAK study. Lancet. 1989;1:175-179.
  11. Thijs VN, Albers GW. Symptomatic intracranial atherosclerosis: outcome of patients who fail antithrombotic therapy. Neurology. 2000;55:490-497.
  12. Akins PT, Pilgram TK, Cross DT, 3rd, Moran CJ. Natural history of stenosis from intracranial atherosclerosis by serial angiography. Stroke. 1998;29:433-438.
  13. Callahan AS, 3rd, Berger BL, Beuter MJ, Devlin TG. Possible short-term amelioration of basilar plaque by high-dose atorvastatin: use of reductase inhibitors for intracranial plaque stabilization. J Neuroimaging. 2001;11:202-204.
  14. Ozgur HT, Kent Walsh T, Masaryk A, Seeger JF, Williams W, Krupinski E, Melgar M, Labadie E. Correlation of cerebrovascular reserve as measured by acetazolamide-challenged SPECT with angiographic flow patterns and intra- or extracranial arterial stenosis. AJNR Am J Neuroradiol. 2001;22:928-936.
  15. Webster MW, Makaroun MS, Steed DL, Smith HA, Johnson DW, Yonas H. Compromised cerebral blood flow reactivity is a predictor of stroke in patients with symptomatic carotid artery occlusive disease. J Vasc Surg. 1995;21:338-345.
  16. Yonas H, Pindzola RR, Meltzer CC, Sasser H. Qualitative versus quantitative assessment of cerebrovascular reserves. Neurosurgery. 1998;42:1005-1012.
  17. Caplan LR, Hennerici M. Impaired clearance of emboli (washout) is an important link between hypoperfusion, embolism, and ischemic stroke. Arch Neurol. 1998;55:1475-1482.
  18. Awad IA, Little JR, Furlan AJ. Conversion of an intracranial arterial stenosis to a symptomatic occlusion after EC/IC bypass surgery. Neurosurgery. 1983;13:734.
  19. Awad I, Furlan AJ, Little JR. Changes in intracranial stenotic lesions after extracranial- intracranial bypass surgery. J Neurosurg. 1984;60:771-776.
  20. Clark WM, Barnwell SL, Nesbit G, O'Neill OR, Wynn ML, Coull BM. Safety and efficacy of percutaneous transluminal angioplasty for intracranial atherosclerotic stenosis. Stroke. 1995;26:1200-1204.
  21. Higashida RT, Tsai FY, Halbach VV, Barnwell SL, Dowd CF, Hieshima GB. Interventional neurovascular techniques in the treatment of stroke--state-of-the-art therapy. J Intern Med. 1995;237:105-115.
  22. Takis C, Kwan ES, Pessin MS, Jacobs DH, Caplan LR. Intracranial angioplasty: experience and complications. AJNR Am J Neuroradiol. 1997;18:1661-1668.
  23. Terada T, Higashida RT, Halbach VV, Dowd CF, Nakai E, Yokote H, Itakura T, Hieshima GB. Transluminal angioplasty for arteriosclerotic disease of the distal vertebral and basilar arteries. J Neurol Neurosurg Psychiatry. 1996;60:377-381.
  24. Connors JJ, 3rd, Wojak JC. Percutaneous transluminal angioplasty for intracranial atherosclerotic lesions: evolution of technique and short-term results. J Neurosurg. 1999;91:415-423.
  25. Marks MP, Marcellus M, Norbash AM, Steinberg GK, Tong D, Albers GW. Outcome of angioplasty for atherosclerotic intracranial stenosis. Stroke. 1999;30:1065-1069.
  26. Mori T, Fukuoka M, Kazita K, Mori K. Follow-up study after intracranial percutaneous transluminal cerebral balloon angioplasty. AJNR Am J Neuroradiol. 1998;19:1525-1533.
  27. Nahser HC, Henkes H, Weber W, Berg-Dammer E, Yousry TA, Kuhne D. Intracranial vertebrobasilar stenosis: angioplasty and follow-up. AJNR Am J Neuroradiol. 2000;21:1293-1301.
  28. Mori T, Kazita K, Mori K. Cerebral angioplasty and stenting for intracranial vertebral atherosclerotic stenosis. AJNR Am J Neuroradiol. 1999;20:787-789.
  29. Mori T, Mori K, Fukuoka M, Arisawa M, Honda S. Percutaneous transluminal cerebral angioplasty: serial angiographic follow-up after successful dilatation. Neuroradiology. 1997;39:111-116.
  30. George CJ, Baim DS, Brinker JA, Fischman DL, Goldberg S, Holubkov R, Kennard ED, Veltri L, Detre KM. One-year follow-up of the Stent Restenosis (STRESS I) Study. Am J Cardiol. 1998;81:860-865.
  31. Huang P, Levin T, Kabour A, Feldman T. Acute and late outcome after use of 2.5-mm intracoronary stents in small (< 2.5 mm) coronary arteries. Catheter Cardiovasc Interv. 2000;49:121-126.
  32. Morice MC, Bradai R, Lefevre T, Louvard Y, Dumas P, Loubeyre C, Piechaud JF. Stenting small coronary arteries. J Invasive Cardiol. 1999;11:337-340.
  33. Gomez CR, Misra VK, Liu MW, Wadlington VR, Terry JB, Tulyapronchote R, Campbell MS. Elective stenting of symptomatic basilar artery stenosis. Stroke. 2000;31:95-99.
  34. Levy EI, Horowitz MB, Koebbe CJ, Jungreis CC, Pride GL, Dutton K, Purdy PD. Transluminal stent-assisted angioplasty of the intracranial vertebrobasilar system for medically refractory, posterior circulation ischemia: early results. Neurosurgery. 2001;48:1215-1223.
  35. Mori T, Kazita K, Chokyu K, Mima T, Mori K. Short-term arteriographic and clinical outcome after cerebral angioplasty and stenting for intracranial vertebrobasilar and carotid atherosclerotic occlusive disease. AJNR Am J Neuroradiol. 2000;21:249-254.
  36. Ramee SR, Dawson R, McKinley KL, Felberg R, Collins TJ, Jenkins JS, Awaad MI, White CJ. Provisional stenting for symptomatic intracranial stenosis using a multidisciplinary approach: Acute results, unexpected benefit, and one- year outcome. Catheter Cardiovasc Interv. 2001;52:457-467.
  37. Lang J. Clinical anatomy of brainstem vessels. New Haven: Miles Pharmaceutical; 1981.
  38. Levy EI, Hanel RA, Bendok BR, Boulos AS, Hartney ML, Guterman LR, Qureshi AI, Hopkins LN. Staged stent-assisted angioplasty for symptomatic intracranial vertebrobasilar stenosis. J Neurosurg. 2002;97:1294-1301.


Reprinted with permission from Mohr JP, Choi DW, Grotta JC, Weir B, Wolf PA (eds): STROKE: PATHOPHYSIOLOGY, DIAGNOSIS, AND MANAGEMENT (4th edition), pp. 1475-1520 (chapter 78), Copyright Elsevier 2004. Permission has been granted to reproduce this material in online electronic format for non-exclusive world English rights.

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