CHAPTER 355 Intracranial Occlusive Disease
Intracranial Atherosclerosis
Epidemiology
About 750,000 people in the United States suffer ischemic cerebrovascular events each year, and 8% to 10% of these events have been attributed to intracranial atherosclerosis. Stroke secondary to intracranial atherosclerosis has been estimated to occur in 56,000 to 90,000 people each year in the United States.1,2 Moreover, intracranial atherosclerosis accounts for a larger percentage, up to 26%, of patients who develop stroke in the ethnic subgroups of Asian, African American, and Hispanic people.3–5 Analysis of the North American Symptomatic Carotid Endarterectomy Trial (NASCET) population found mild intracranial atherosclerosis (wall irregularities without stenosis) in 26.9% of the patients, moderate disease (<50% stenosis) in 5.8%, and severe stenosis (>50% stenosis) in 0.5%.6 Most studies evaluate symptomatic intracranial arteriosclerosis; therefore, there are few data available to estimate the overall incidence of asymptomatic intracranial disease in the population.
Several large series have provided demographic information on the symptomatic patient population. The Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial demonstrated that the at-risk population for developing intracranial arteriosclerosis shares common cardiovascular risk factors. The mean age of these patients was 63.5 years, with a male predominance (62%). Associated risk factors included prior cardiac ischemic events, prior cerebrovascular accidents, hypertension, diabetes, hyperlipidemia, and smoking.2 In some studies, about 50% of disease pathology presents in the internal carotid artery (ICA), whereas the remaining cases are distributed throughout the remaining cerebral circulation.7
Intracranial atherosclerosis has been attributed to account for about 22% to 26% of ischemic strokes in the Asian population, 6% to 29% of cerebrovascular events in blacks, and up to 11% of infarcts in Hispanics.3–5,8–10 Although the overall incidence was higher in men, in subgroup analysis women had an 85% greater risk for developing recurrent cerebrovascular events compared with men. This apparent increased risk may be attributed to associated socioeconomic factors.11
Pathophysiology
Intracranial atherosclerosis can lead to an ischemic cerebrovascular event through several differing processes: (1) hypoperfusion, (2) thrombosis at the site of stenosis, (3) thromboembolism, and (4) direct occlusion of small perforating vessels.12–17 Depending on the underlying cause, the clinical presentation may vary from an acute ischemic deficit due to embolic or thrombotic sources to intermittent neurological symptoms from hypoperfusion. This chapter mainly discusses cerebral hypoperfusion secondary to intracranial atherosclerotic lesions; acute ischemic events are discussed in Chapter 344.
Natural History and Medical Management
A meta-analysis by Komotar and colleagues reviewed the natural history of intracranial atherosclerosis based on the identified pathologic vessel and found an annual ipsilateral risk of ischemic events ranging from 3.1% to 8.1% for the ICA.18 In the vertebrobasilar circulation, with a minimum stenosis of 40%, they found the annual risk for stroke in the same vasculature distribution ranged from 0% to 8.7% and annual overall stroke risk of between 3% and 14.3%. For the middle cerebral artery (MCA), the annual ipsilateral stroke risk ranged from 0% to 7.8%, and overall stroke risk ranged from 0% to 5%. The results of this retrospective study, in addition to those of several prospective series, are consistent with the findings from the WASID trial supporting that the risk for ischemic events in the posterior circulation does not exceed that of the anterior circulation.2 However, these investigators did find an increased risk for mortality from posterior circulation and ICA ischemic events compared with the MCA distribution. The discrepancy in mortality rate may simply reflect the relative importance of the neuroanatomic regions supplied by these vessels.
In terms of medical management, several retrospective studies have shown benefit of warfarin sodium (Coumadin) over aspirin to decrease the risk for recurrent ischemic events.19 In one series, patients treated with warfarin after a transient ischemic attack (TIA) or stroke had a 7% risk for stroke or stroke-related death with 14.7 months of follow-up, whereas patients treated with aspirin experienced a 24% risk for stroke or mortality with 19.3 months of follow-up.19 The same retrospective series found that warfarin (3.6% per year) was favorable over aspirin (10.4% per year) in the reduction of cerebrovascular events.
The prospective, randomized WASID study group, however, did not corroborate the prior retrospective conclusions. No statistically significant differences in cerebrovascular event rates between warfarin and high-dose aspirin were found. However, the study did observe a higher risk for noncerebral major hemorrhage from warfarin, not supporting the use of warfarin over high-dose aspirin.2
Recently, a better understanding of the disease evolution has been achieved through additional prospective clinical studies evaluating medical therapy. A prospective, although small, series compared aspirin and warfarin in the treatment of MCA stenosis and found equivocal results looking at the incidence of stroke reduction.20 The Groupe dEtude des Stenoses Intra-Craniennes Atheromateuses Symptomatiques (GESICA) study evaluated 102 nonrandomized patients prospectively treated with varying combinations of antiplatelet and anticoagulant therapies. Even with medical therapy, 38.2% of their sample developed recurrent ischemic events or TIAs within the 23.5 months of follow-up.21 This alarmingly high rate of disease progression was emphasized by a retrospective review that found a medical failure rate of 47.7% for the prevention of TIA or stroke.22 These high rates of recurrent cerebrovascular events even on medical therapy certainly prompt an urgency to identify optimal medical and adjuvant surgical therapies for high-risk patients.
For asymptomatic patients, there is no consensus on optimal management guidelines. The position statement from the American Society of Neuroradiology (ASNR) in 2005 highlighted the uncertainty of treating asymptomatic stenosis.23 The risk for stroke is thought to be lower in asymptomatic patients with MCA stenosis, and the incidence has been estimated at 1.4% to 2.8% per year.24
Risk Factors and Progression
For symptomatic lesions, recent large and prospective studies have helped delineate some of the risk factors contributing to progressive disease. Some authors have found a trend among female gender, extent of intracranial stenosis, and additional presence of asymptomatic stenosis to be associated with a higher risk for future events.25 Progressive MCA stenosis, as evaluated by transcranial Doppler (TCD) studies, appears to be an independent risk factor for increased stroke risk because 32.5% of patients with progressive disease had a stroke by 26 months of follow-up.25 Other series have supported that severe stenosis (>70% stenosis), female gender, National Institutes of Health Stroke Scale score greater than 1, concurrent diabetes, borderline body mass index values, hyperlipidemia, white ethnicity, and presence of hemodynamic stenosis increase the risk for stroke.19,21,22 The GESICA study found that the presence of hemodynamic instability, determined clinically, increased the risk for cerebrovascular events from 31.7% to 60.7%.21 As we identify more high-risk traits in patients, we can better stratify patients into appropriate management protocols.
Radiographic Evaluation
Patency of Vessels
Indirect estimates of flow may be extrapolated from varying imaging modalities. MRA and CTA both provide excellent detail regarding the caliber of vessels, although MRA has been shown to overestimate the degree of stenosis in some cases.26 Correlation between MRI blood volume flow and angiographic flow suggested that MRI may overestimate stenosis in the cavernous ICA, at the distal ICA bifurcation, and at the MCA bifurcation secondary to turbulent flow.26 However, looking at the source images as opposed to the reconstructions can reduce this error. In some series, time-of-flight MRA using 1.5-Tesla MRI had a sensitivity of 90% to 95%, a specificity of 95%, a positive predictive value (PPV) of 84% to 86%, and a negative predictive value (NPV) of 97% to 98%. The diagnostic accuracy ranged from 93% to 95% compared with digital subtraction angiography. However, other authors have postulated that CTA is better than both MRA and TCD to assess intracranial stenosis.27
The WASID trial found that noninvasive techniques carried a 33% false-positive rate in determining more than 50% stenosis.19 The Stroke Outcomes and Neuroimaging of Intracranial Atherosclerosis (SONIA) trial enrolled 407 patients to determine the reliability of using TCD or MRA in determining the extent of stenosis. These investigators concluded that TCD had a PPV of 36% and an NPV of 86%, whereas MRA had a PPV of 59% and an NPV of 91%.28 These noninvasive techniques were sufficiently accurate to exclude more than 50% stenosis, but further confirmatory studies were needed to characterize the stenosis. Transcranial color sonography (TCCS) was not ideal to assess MCA stenosis and was less reliable when the ICA had greater than 50% stenosis. Overall, there is still much debate regarding the use of noninvasive techniques to ascertain intracranial stenosis. However, CTA, MRA, and ultrasound techniques have been consistently reliable in the first-line evaluation of stenosis. Currently, their specificity and PPV are not reliable enough to replace invasive evaluations, but with improved technology such as 3-Tesla MRI, the need for invasive procedures may eventually diminish.
Perfusion
Varying modalities have been used to quantify cerebral perfusion and flow-related changes within the brain parenchyma. Perfusion studies include PET scans, SPECT scans, xenon CT perfusion studies, CT perfusion, and perfusion MRIs (Fig. 355-1).29 These studies permit the extrapolation of CMRO2, OEF, and CBF and provide information on the perfusion of the brain. Varying techniques have been validated through separate studies, but no standard has been established as preferable to others. Individual modalities are discussed in further detail in other chapters.
Mendelowitsch identified hemodynamic instability using SPECT in 65 patients and retrospectively monitored them after they received superficial temporal artery (STA)-MCA bypasses.30 He noted that 88% of patients had neurological function improvement. Other studies have used PET to select patients for revascularization procedures and have correlated clinical improvement with improved radiographic findings as well.31 The Japanese EC-IC Bypass Trial (JET) used SPECT imaging with an acetazolamide challenge to calculate hemodynamic parameters in patients. They used a technique of three-dimensional stereotactic surface projections with stereotactic extraction estimation to objectively quantify hemodynamic instability.32
Currently, the ongoing Carotid Occlusion Surgery Study (COSS) employs measuring OEF by PET.33
Operative Treatment
Surgical Technique
Open surgical revascularization has diminished significantly in popularity since the publication of the JET study.34 However, the procedure and its variations are still beneficial to carefully selected patients. Since the first STA-MCA procedure was described by Yasargil in 1969,35 many variations have been reported. Many of these variations have been developed in dealing with complex cerebral aneurysms and skull base neoplasms in which vessel sacrifice is required. These variations include anastomoses between the bilateral anterior cerebral arteries; occipital artery–to–posterior, inferior cerebral artery (PICA), anterior and inferior cerebral artery (AICA). Others includes PICA to PICA, vertebral artery to PICA, STA to SCA or PCA, subclavian artery to PCA, PCA to SCA, and even a tandem occipital artery to AICA and PICA anastomoses.36 Essentially any two vessels than can be liberated and approximated can be used to create an anastomosis. In terms of the surgical treatment of intracranial atherosclerosis, the main bypass procedure remains the STA-MCA bypass.
Operative Technique
The operative technique (see Video 355-1) proceeds as follows.
Under loupe magnification or the microscope, the skin is incised over the STA. Using sharp technique, the subcutaneous layer is divided until the layer harboring the STA is encountered. Bleeding points from the skin edges are carefully coagulated using very fine jeweler bipolar forceps. Dissection proceeds along the entire course of the STA until it has been dissected free of the subcutaneous tissues. Using fine bipolar forceps, small branches from the STA are coagulated and divided. A self-retaining retractor is used to retract the skin edges, and the galea surrounding the STA is divided using a needle-tip Bovie, leaving a generous soft tissue cuff. With the STA completely dissected free, it is retracted laterally and protected under a papaverine-soaked cottonoid (Fig. 355-2).
The underlying temporalis muscle and fascia are divided with electrocautery in line with the incision and reflected laterally with the self-retaining retractors. Two bur holes are placed at the inferior and superior limits of the planned craniotomy flap. An elliptical bone flap is then fashioned and removed. The location of the bone flap should be centered about 6 to 7 cm above the external auditory meatus. Alternatively, a mathematical approach to the ideal location of a recipient vessel has been recently published that may permit a more localized craniotomy.37 Dural tenting sutures are placed along the bone edges. At this point, the STA is centered over the craniotomy area; if undue tension is apparent, the STA should be freed further by expanding the dissection proximally and distally. A redundant STA that can be placed over the desired area without tension or stretching is the goal.
At this point, the dura is opened in a cruciate manner, with care taken not to disturb or injure any naturally developed transdural collaterals. Further, in the event that the middle meningeal artery (MMA) is providing significant dural collaterals to the brain, the incision is modified to preserve the MMA. Under the operating microscope and using microsurgical technique, the brain surface is inspected for a suitable recipient M4 branch. Once identified, the arachnoid over the sulcal area is opened (Fig. 355-3
