Stroke & Vascular Disorders
Cerebellar infarction and cerebellar hemorrhage
Oct. 26, 2023
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Toll Free (U.S. + Canada): 800-452-2400
US Number: +1-619-640-4660
Support: service@medlink.com
Editor: editor@medlink.com
ISSN: 2831-9125
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Cerebral vascular insufficiency, typically caused by extra- or intracranial steno-occlusive disease, is the leading cause of ischemic stroke. Surgical treatment options for cerebral vascular insufficiency due to extracranial steno-occlusive disease include endarterectomy, and endovascular treatment options include angioplasty with or without stent placement. Surgical treatment options for cerebral vascular insufficiency due to intracranial steno-occlusive disease include cerebral revascularization procedures, such as extracranial to intracranial bypass (EC-IC bypass); endovascular treatment options include angioplasty with or without stent placement as well as mechanical thrombectomy. In this updated article, etiologies of cerebral vascular insufficiency are reviewed, and revascularization techniques are discussed.
• Cerebral vascular insufficiency with or without stroke is a prevalent cause of neurologic morbidity and mortality worldwide. | |
• Many steno-occlusive lesions, particularly when refractory to medical management, can be managed by endovascular or surgical revascularization. | |
• Mechanical thrombectomy has become the standard of care for selected patients with acute large cerebral artery occlusion. | |
• Further research is required to better define the indications and the limitations of cerebral revascularization techniques. |
Descriptions of early attempts of surgical embolectomy for the treatment of brain ischemia appeared in the literature in the 1950s (109; 24). Microsurgical reconstruction of brain arteries, ie, cerebral bypass surgery, became available following introduction of the operating microscope in the 1960s (113). Indications for intracranial revascularization procedures have subsequently been refined, and surgical techniques have considerably evolved over the following decades.
The association between extracranial carotid pathology and ipsilateral ischemic stroke was recognized in the early 1900s (54; 60), and carotid endarterectomy for stroke prevention was introduced only in the second half of the 20th century (35; 43). There has been an exponential growth in the application of carotid endarterectomy for the treatment of carotid atherosclerotic disease, with over 30,000 carotid endarterectomies being carried out annually in the United States by the 1980s.
Endovascular cerebral revascularization began with the introduction of percutaneous dilating angioplasty in the 1960s (38). A decade later, percutaneous transluminal angioplasty was adopted (51). Carotid artery stenting became available mid-1990s (37). Stents have since been used in nearly every segment of the cerebral circulation and for various indications.
Intraarterial installation of thrombolytic drugs directly into the occluding thrombus for the urgent revascularization of patients suffering from cerebral artery occlusions became available in the 1980s (116; 117). However, intra-arterial thrombolysis remained limited by its comparatively low ability to re-establish flow, which contributed to the development of endovascular mechanical thrombectomy. Initially, the occluding particle was retrieved using various types of snares. However, snares were technically challenging to use and were, therefore, progressively replaced by more trackable and more efficient devices, so-called stent retrievers (aka "stentrievers") (44). Although first-generation stent retrievers allowed an increase in recanalization rates, their ability to improve functional outcomes in patients suffering from large cerebral artery occlusions remains unproven (102; 11; 12). The turning point for mechanical thrombectomy occurred in 2015 when 5 multicenter, open-label randomized controlled trials (MR CLEAN, ECAPE, SWIFT PRIME, EXTED-IA, and REVASCAT) unequivocally demonstrated that mechanical thrombectomy with second-generation stent retriever devices was superior to standard treatment with intravenous thrombolysis alone (09; 16; 47; 64; 97). Since then, indications for mechanical thrombectomy continue to expand, and clot retrieval techniques continue to be refined.
General concepts. Atherosclerosis is the primary cause of cerebral vascular insufficiency. Nonatherosclerotic etiologies include various types of inflammatory disease as well as trauma. Generally, any lesion capable of producing cerebral vascular insufficiency, with or without ischemia or infarction, does so by virtue of a combination of distinct attributes, each with its own pathogenic implications (Table 1).
Attribute |
Defining criterion |
Influencing variables |
Hemodynamic impact |
Degree of bulk flow alteration downstream from the lesion |
Degree of stenosis |
Emboligenicity |
Propensity of the lesion to generate thromboembolism |
Endothelial integrity |
Branch involvement |
Involvement of arterial branches by the lesion, through extension or embedment |
Competing target tissues |
Hemodynamic impact. The hemodynamic impact of a stenotic lesion depends on the reduction of bulk flow in the affected artery and, consequently, the reduction of perfusion in its vascular bed. From a clinical point of view, the patient may remain asymptomatic, may suffer from hypoperfusion symptoms, or may develop ischemic stroke. The appearance of clinical manifestations depends on factors such as metabolic needs of the concerned territory or competence of collateral circulation.
The flow of fluids through a tubular entity such as a cerebral artery can be approximated by Poiseuille’s Law, which states that the flow depends on the viscosity of the fluid, the pressure gradient along the tube, the length of the tube, and the diameter of the tube. It is important to remember the strong impact of caliber variations, meaning, for instance, that reducing the tube’s diameter by half (50% stenosis) decreases the flow rate by 16-fold (r4). It remains challenging to quantify bulk arterial flow with sufficient accuracy for clinical application, despite the introduction of techniques like quantitative magnetic resonance angiography (32). Therefore, surrogate measurements, such as “degree of stenosis” (ie, the maximal reduction in vascular cross-sectional diameter caused by a lesion, typically expressed as a percentage), are used in clinical practice to estimate the severity of a stenotic lesion and to determine whether or not a revascularization procedure is indicated.
Alternatively, the hemodynamic impact of a stenotic cerebrovascular lesion (as well as the effects of revascularization) can be estimated quantitatively or semi-quantitatively by a range of advanced imaging techniques that include computed tomography perfusion imaging, magnetic resonance perfusion imaging, and positron emission tomography (112; 70; 21).
Emboligenicity. Stenotic lesions can also produce downstream ischemia by embolus formation. This phenomenon can occur already at non-flow-limiting degrees of stenosis. From a clinical point of view, the patient may remain asymptomatic (“silent emboli”) or develop neurologic impairment, depending on the location and size of the thromboembolic stroke.
As the lumen of the vessel decreases, there is a shift from laminar to turbulent flow. Turbulent flow is associated with disturbed hemostasis by increased platelet aggregation (ie, "white clot" formation), resulting in thrombo-emboli formation. As flow compromise progresses, turbulence intensifies, and downstream perfusion is reduced. This adds another dimension to the disturbance of hemostasis, hence, the risk for stroke: sluggish flow as a prethrombotic state (ie, "red clot" formation). Finally, occlusion is followed by the appearance of a stagnant column of flow distal to the lesion, with its consequent downstream hemodynamic compromise.
The propensity of a stenotic lesion to generate thromboembolism also depends on its endothelial surface integrity, morphology (ie, composition), and stability. Lesions with smooth surface and endothelial integrity have comparatively little emboligenic potential. Disruption of endothelial continuity results in exposure of the subendothelial thrombogenic surfaces, thereby, increasing the likelihood of thromboembolism.
Branch involvement. Cerebrovascular lesions often involve branching arterial segments. In certain arterial segments, this is usually of no clinical consequence. Occlusion of the external carotid artery, for instance during carotid endarterectomy, is generally well tolerated. In other cases, such as internal carotid artery bifurcation, the involvement of branching arterial segments (middle cerebral artery and anterior cerebral artery) must be scrutinized differently because of additional variables influencing the benefit-to-risk assessment. Similarly, collateral branches embedded into the lesion itself represent a challenge, both from the diagnostic and the therapeutic point of view.
Carotid stenosis. Extracranial carotid atherosclerosis accounts for 15% to 20% of ischemic strokes in the United States. The disease is more prevalent in men, and its prevalence steadily increases with age (40; 34). Treatment options include medical management, carotid endarterectomy, and endovascular balloon dilatation (ie, angioplasty) with or without stent placement. Although early clinical trials focused on the benefits of carotid endarterectomy versus maximal medical management, more recent research has come to concentrate on the similarities and differences between carotid endarterectomy and endovascular alternatives. Broadly, current guidelines recommend carotid endarterectomy or angioplasty in combination with stent placement for symptomatic carotid stenosis greater than 50% and for asymptomatic carotid stenosis greater than 70% (13).
Symptomatic carotid stenosis. The NASCET trail remains the most important study to guide decision-making (84). When the trial was terminated during interim analysis, 659 symptomatic patients with greater than 70% stenosis had been randomized to either a combination of medial management and carotid endarterectomy or to medical management alone. With 24 months of mean follow-up, ipsilateral strokes had occurred in 26% of the nonsurgical cohort, compared to 9% of patients who had undergone carotid endarterectomy. Statistically significant outcome benefits included stroke in any territory, major stroke, and major stroke or death from any cause. By 3 months following carotid endarterectomy, the benefits of carotid endarterectomy were evident. Perioperative morbidity and mortality were just under 6%. Subsequent meta-analyses of major symptomatic carotid stenosis trials (NASCET, ECST, and VASST) demonstrated marginal stroke prevention benefit of carotid endarterectomy for patients with 50% to 69% stenosis, equivalent outcomes compared to medical management for patients with mild stenosis (30% to 49%), and worse outcomes with surgery for patients with minimal stenosis (less than 30%) (84; 75; 07; 94).
Asymptomatic carotid stenosis. In the ACAS and the ACST trials, asymptomatic patients with greater than 60% carotid stenosis were randomized either to medical management combined with carotid endarterectomy or to medical management alone (06; 57). ACAS found a 5.9% absolute risk reduction in patients undergoing carotid endarterectomy (11% vs. 5.1%), and ACST similarly found a 5.4% absolute risk reduction in patients treated by carotid endarterectomy (11.8% vs. 6.4%). Of note, the benefits of surgery over medical management depend on a morbidity and mortality rate below 3% for carotid endarterectomy.
Carotid artery stenting. The CREST trial demonstrated that carotid artery angioplasty with stent placement is at least equally effective as carotid endarterectomy, with the exception of patients 70 years of age or older who had a lower incidence of perioperative strokes with carotid endarterectomy when compared to angioplasty with stent placement (14; 13).
Medical management. With the advent of statins, aggressive dyslipidemia treatment, and modern antiplatelet agents, there is ongoing debate whether the results of these pivotal trials remain valid. The CREST-2 is currently enrolling asymptomatic patients with greater than 70% stenosis to separately compare carotid endarterectomy to modern medical management alone and carotid artery balloon-dilatation in combination with stent placement to modern medical management alone (estimated study completion: December 2022) (59).
Transcarotid artery revascularization. This procedure combines percutaneous common carotid artery puncture, proximal reverse flow embolic protection, and balloon-dilatation with stent placement. Conceptually, this strategy addresses several key shortcomings of both endovascular and surgical carotid revascularization. In the absence of randomized trials, there have been promising initial results with this technique, for instance regarding the reduction of the 1-year risk for ipsilateral stroke and death (67).
Carotid artery angioplasty with stent placement is an appealing alternative for patients with a greater than average perioperative carotid endarterectomy risk profile because it is a technically simple procedure that can be completed in 15 to 20 minutes under local anesthesia.
Carotid artery angioplasty with stent placement carried a perioperative stroke and death rate of 7% to 9% in early experience. However, following the introduction of embolic protection devices, registries and clinical trials demonstrated a progressive decline in complication rates (55; 26), which paved the way to a more rigorous comparison of carotid artery angioplasty with stent placement and carotid endarterectomy (14; 10; 62; 96).
The 30-day major adverse cardiovascular event rates reported by the various registries and studies of carotid artery stenting, organized chronologically by the year of publication, illustrate the continued decremental trend obs...
The pivotal studies (ie, CREST) demonstrated clinical equipoise between carotid artery angioplasty with stent placement and carotid endarterectomy in symptomatic patients, both in the short and long term (ie, 10-year follow up) (14; 15). Besides that, these trials suggested that:
The issue of carotid revascularization of asymptomatic patients is just as controversial for carotid artery stenting as it has been for carotid endarterectomy (due to the lesser margin of benefit when compared to patients with symptomatic carotid stenosis). Still, preliminary data suggest that the benefits of carotid artery stenting may be comparable to those of carotid endarterectomy (93). Presently, CREST-2 is a double parallel, multicenter, randomized, observer-blinded study that explores the potential benefit of adding either carotid endarterectomy or carotid artery stenting to maximal medical therapy in asymptomatic patients with greater than 70% stenosis (59). Finally, carotid artery stenting also remains an appealing alternative to carotid endarterectomy for lesions that are not readily accessible to surgery (ie, requiring much more complex procedures than the standard carotid endarterectomy, for instance, in patients where the lesions is located above the angle of the mandible).
With regards to nonatherosclerotic lesions, such as traumatic injuries (eg, dissections), congenital vasculopathies (eg, fibromuscular dysplasia), and proliferative stenoses (eg, radiation), there remains a lack of large prospective clinical trials. Although many of these conditions have been the subject of sporadic reports on the use of carotid artery stenting for treatment, it remains difficult to make general recommendations. It seems, therefore, reasonable to have an individualized therapeutic strategy for these patients, many of whom may well benefit from carotid artery stenting, particularly when symptoms are persistent despite maximal medical therapy.
Extracranial vertebrobasilar circulation. Vertebral pathology causing brain ischemia is associated with a 90-day risk of stroke of 25% to 30% following any index event (81; 52; 53), and approximately 15% to 50% of patients who present with vertebrobasilar insufficiency have either an underlying hemodynamically significant lesion or artery-to-artery embolisms (17). Treatment options for vertebrobasilar insufficiency have not been studied as extensively as for carotid artery stenosis. In general, these lesions are often challenging to access by means of open surgery, and endovascular techniques are, therefore, often preferred for revascularization of lesions that involve the subclavian or the extracranial portion of the vertebral arteries.
Subclavian and vertebral bypass. Bypass surgery for vertebrobasilar insufficiency has become exceptional given the advancements in endovascular technology. Still, bypass procedures remain a proven treatment option for vertebrobasilar insufficiency as seen with vertebral artery occlusion or subclavian steal syndrome.
“Subclavian steal” is defined as reversal on vertebral arterial flow. This syndrome is typically due to stenosis or occlusion of the first segment of the subclavian artery. Although only 7% of patients with subclavian steal and an arm pressure difference greater than 20 mmHg are symptoms of vertebrobasilar circulation ischemia, typically the pressure difference reaches at least 40 mmHg (68). Endovascular balloon-dilatation and stent placement have become the first-line treatment, but subclavian artery to carotid artery transposition or a carotid to subclavian artery bypass remain proven alternatives, particularly in cases where the lesion cannot be crossed endovascularly (27). Subclavian and vertebral bypass surgery commonly utilizes the occipital artery, which is anastomosed to the extradural vertebral artery, the posterior inferior cerebellar artery, or the posterior cerebral artery branch, depending on the patient’s site of steno-occlusive disease (56; 58; 104). Endarterectomy of the vertebral artery has also been described, but this procedure is no longer used in routine practice given the availability of endovascular angioplasty and stenting options.
Subclavian and vertebral artery angioplasty and stenting. Although the application of percutaneous transluminal angioplasty for the management of subclavian artery steno-occlusive lesions dates back to the 1980s (08; 74; 107), there remains an ongoing debate in the literature regarding angioplasty versus stenting, without any clear settlement based on the existing information (61; 01). Overall, there are probably lesions that can effectively be treated by angioplasty alone, but maintaining patency in more complex or resilient lesions likely requires stent placement. This seems particularly true in patients with occluded subclavian arteries, many of whom present with symptoms of neurologic (ie, vertebrobasilar) or cardiac (ie, internal mammary artery-coronary) steal (73; 46; 95).
Lesions of the vertebral artery are prevalent, and a vertebral artery stenoses that causes 50% or more diameter reduction carries a stroke risk similar to carotid pathology (81; 31). Stroke risk is highest during the weeks that follow the index event (ie, acute ischemic stroke or transient ischemic attack) (53). Reports on vertebral artery angioplasty and stenting date back to the late 1990s (19; 71). Despite multiple reports of low rates of periprocedural complications and high efficiency in addressing refractory vertebrobasilar insufficiency in particular (105), there remains ongoing skepticism about the effectiveness of the technique (30; 72). Also, in-stent restenosis remains definitively a risk, even if the severity of restenosis is often not sufficient to require additional intervention, and technologic advances (eg, drug-eluding stents and balloons) likely continue to lower its incidence (85; 18).
Nonatherosclerotic lesions of the extracranial vertebral artery are less frequent, the most pervasive being traumatic dissection, typically at the V1-V2 or V2-V3 interface. Just as in the carotid territory, a majority of dissections heal spontaneously without the need for intervention. However, there are patients whose symptoms prove refractory to medical treatment, or whose lesions cause flow compromise in the context of suboptimal contralateral collateral support, and these patients should definitively be consideration for intervention. Stenting of dissection of the extracranial vertebral artery has been shown to be safe and effective, although the existing literature remains scarce (89; 28; 29; 25; 45).
Intracranial atherosclerosis. Intracranial atherosclerosis is the most common cause of acute ischemic stroke worldwide, and approximately 50,000 to 100,000 patients per year suffer from acute ischemic stroke due to intracranial atherosclerotic lesions in the United States. Its prevalence approximates 13% to 15% in the overall population, and prevalence is even higher in African-Americans, Japanese, Chinese, and Hispanics, possibly due to a disproportionate prevalence of uncontrolled risk factors, such as arterial hypertension, in these populations (66; 103; 39; 110). Intracranial atherosclerosis carries considerable risk for acute ischemic stroke following any index event, irrespective of any chosen medical therapy. In fact, in 2 prospective randomized studies of stenting versus aggressive medical therapy (ie, SAMMPRIS and VISSIT), the patients in the medical groups still accrued acute ischemic stroke rates of approximately 5% to 9% during the first 30 days following randomization, and 9% to 12% during the first year of follow-up (23; 22; 36; 114).
Unlike internal carotid artery or vertebral artery lesions, there is considerable variability among intracranial atherosclerotic lesions, particularly in relation to their location and relationship to other intracranial arteries.
Intracranial atherosclerosis lesions can be differentiated on the basis of 3 attributes:
Accordingly, not all intracranial atherosclerosis lesions are equivalent in terms of risk (both natural and procedural) and therapeutic approach (ie, either medical or interventional).
(A) Oblique, and (B) lateral views of 3 severely stenotic tandem lesions located in the same internal carotid artery: intraosseous, transitional, and subarachnoid. (C) Anteroposterior and (D) lateral views of the control angiog...
Lack of discrimination between different types of intracranial atherosclerosis lesions potentially explains unsuccessful outcomes of certain clinical trials (ie, SAMMPRIS and VISSIT) (23; 36; 114), and granular differences in the morphology of intracranial atherosclerosis lesions have been shown to considerably influence the outcomes of percutaneous transluminal angioplasty and stenting (Table 2) (78; 79; 80).
Prior to 2011, more than 80 reports in the literature suggested that percutaneous transluminal angioplasty and stenting could be applied to the treatment of intracranial atherosclerosis lesions with reasonable safety, although there were concerns about high restenosis rates and uncertainty about efficacy (78; 79; 80; 33; 41; 42; 115; 101; 111). The results of 2 pivotal subsequent studies, SAMMPRIS and VISSIT, changed the prevailing enthusiasm for stenting of intracranial atherosclerosis lesions almost overnight (23; 36; 114). Both studies were stopped prematurely due to the results of interim analyses that uncovered 30-day stroke and death rates that were significantly higher in the patients treated endovascularly (ie, 14.7% and 29.3%, respectively) than in the medical treatment groups (ie, 5.8% and 9.4%, respectively). Interestingly, the stroke rates for the medically treated patients at 1-year follow up were 12.2% and 15.1% respectively, underscoring the seriousness of this condition. Both of these studies have been the subject of criticism, discussions, and controversy, with additional series continuing to appear in the literature (100; 90; 20). Still, SAMMPRIS type medical management has become the first-line treatment option for intracranial atherosclerotic lesions that present with first-time ischemic stroke. The role of endovascular treatment, for instance in patients who suffer from recurrent stroke under SAMMPRIS type medical management, remains to be clarified.
Intracerebral artery lesion | Attribute | Finding | Success | Restenosis |
Type A | Extension | Discrete | 90% | 0% |
Length | < 5 mm | |||
Stenosis (ø) | 70% to 90% | |||
Occlusion | Not | |||
Accessibility | Readily accessible. Straight | |||
Contour | Smooth | |||
Calcification | None | |||
Branch involvement | None | |||
Thrombus | None | |||
Type B | Extension | Tubular | 77% | 31% |
Length | 5 to 10 mm | |||
Stenosis | 90% or greater | |||
Occlusion | Near | |||
Accessibility | Tortuous and | |||
Contour | Irregular | |||
Calcification | Moderate | |||
Branch involvement | Yes. Protectable | |||
Thrombus | Possible | |||
Type C | Extension | Diffuse | 67% | 67% |
Length | Greater than 10 mm | |||
Stenosis | Occlusion | |||
Occlusion | Yes | |||
Accessibility | Tortuous and | |||
Contour | None | |||
Calcification | Severe | |||
Branch involvement | Yes. Not protectable | |||
Thrombus | Yes | |||
|
Cerebrovascular bypass (ie, cerebral blood flow augmentation surgery). Cerebrovascular or intracerebral bypass collectively refers to a wide range of microsurgical techniques used to improve blood flow and oxygenation to the distal cerebral vasculature. These methods include direct (eg, anastomosis of an extracerebral artery to an intracerebral artery) and indirect (eg, apposition of an extracranial artery or vascularized tissue onto the pial surface) techniques. The former method affords immediate augmentation of hemodynamic flow; the latter method requires months to years for collateral vascular connections to develop. Various indirect bypass procedures include encephaloduroarteriosynangiosis (ie, donor = superficial temporal artery), encephalo-myo-synangiosis (ie, donor = temporalis muscle), and omental transposition (ie, donor = vascularized abdominal tissue). In situ bypass involves an anastomosis between 2 intracerebral arteries; this is an uncommon procedure and is outside the scope of this article. Direct cerebral bypass can be further dichotomized into high-flow (eg, anastomosis of external carotid artery to an intracerebral artery using an interposition graft) and low-flow (eg, anastomosis of superficial temporal artery or occipital artery to middle cerebral artery). The superficial temporal artery-middle cerebral artery arterial graft is the most common of the direct procedures and is the focus of this article.
Direct superficial temporal artery to middle cerebral artery (STA-MCA) bypass surgery is typically performed under single antiplatelet medication, the most often under aspirin 81 to 325 mg daily for 5 to 10 days. Angiography provides information about the course and size of the donor (superficial temporal artery or occipital artery) and recipient (middle cerebral artery) arteries; this should be at least 1 mm in diameter. Through the procedure, mean arterial pressure is maintained approximately 10% to 15% above baseline, and osmodiuresis is not used to avoid hypotension. Following exposure, under microscopic visualization, the recipient middle cerebral artery branch on the pial surface is dissected from its arachnoid attachments. Temporary clips are placed on the proximal and distal ends of the recipient artery, and the artery is opened sharply.
A temporary clip is placed on the proximal superficial temporal artery branch, the artery is transected distally and "fish-mouthed" to widen the orifice, and an end-to-side arterial anastomosis is completed. Micro-Doppler and indocyanine green videoangiography are used to verify patency of the graft. Postoperatively, the mean arterial pressure is maintained at baseline or slightly elevated, and aspirin is continued for life. Catheter angiography is performed at 6 to 12 months to verify patency of the graft.
In 1985, the Extracranial/Intracranial Bypass Study Group published a prospective, international, randomized clinical trial to address the question of whether extracranial-to-intracranial (EC-IC) bypass in addition to optimal medical therapy was superior to best medical therapy alone in patients with recently-symptomatic extra- or intracranial athero-occlusive disease (Group EIBS 1985). After an average follow-up period of 55.8 months (and despite an excellent graft patency rate of 96%), the authors found no surgical benefit for bypass surgery as compared to medical management alone (14% increase in relative risk of fatal and nonfatal stroke in surgical as compared to medical group). Further, higher rates of major perioperative ischemic strokes were seen in the surgical group (4.5% vs 1.3%). Outcomes were particularly poor in patients with middle cerebral artery stenosis or occlusion and those with ongoing symptoms. This study was criticized for the lack of hemodynamic criteria used to select patients at particularly high risk of stroke and, therefore, likely to derive the most benefit from surgery. This critical issue was subsequently addressed in the Carotid Occlusion Surgery Study (COSS) (86). The COSS was a prospective, randomized, blinded-adjudicated trial designed to address the question of whether STA-MCA bypass (in addition to best medical therapy) reduced the 2-year risk of ipsilateral ischemic stroke as compared to optimal medical therapy alone. The trial enrolled patients who had recently suffered from symptomatic extracranial internal carotid artery occlusion and who had documented hemodynamic cerebral ischemia (eg, increased oxygen extraction fraction on positron emission tomography). Despite high graft patency rates (98%), the authors found no benefit for surgery (2-year ipsilateral stroke risk = 21% in surgical group vs. 22.7% in medical group; p = 0.8) and a higher rate of perioperative stroke in the surgical group (14.4% vs. 2%, respectively; 95% CI 4.9% to 19.9%). However, a follow-up report detailing the surgical results of COSS and excluding the patients who experienced perioperative strokes (within 30 days of surgery) revealed improved cerebral hemodynamics and lower rates of recurrent ipsilateral ischemic strokes in the surgical group as compared to the medical group (9% vs. 22.7%, respectively, at 2 years) (50). These findings suggest that factors unrelated to the surgery (eg, hemodynamic fragility of the patients involved) were likely responsible for high perioperative stroke rate in the surgical group (92; 91). Taken all together, the EC-IC bypass trial and COSS trial ultimately provided Level I evidence for the lack of benefit of STA-MCA bypass in patients with recently-symptomatic extra- or intracranial athero-occlusive disease.
Moyamoya disease is a rare, progressive cerebrovascular disease defined by a progressive steno-occlusion of unknown etiology that affects the bilateral supraclinoid internal carotid artery and often involves the proximal anterior and middle cerebral arteries as well. The name “moyamoya” means “puff of smoke” in Japanese and describes the look of the tangle of tiny vessels formed in the basal ganglia to compensate for the blockage. Moyamoya disease was first described in Japan and is found in individuals around the world; its incidence is higher in Asian countries than in Europe or North America. The disease primarily affects children, but it can also occur in adults. In children, the first symptom of Moyamoya disease is often stroke, or recurrent transient ischemic attacks (TIA, commonly referred to as “mini-strokes”), frequently accompanied by muscular weakness or paralysis affecting one side of the body. Adults may also experience these symptoms that arise from blocked arteries but more often experience a hemorrhagic stroke due to bleeding into the brain. Other symptoms of Moyamoya disease include headaches, seizures, disturbed consciousness, involuntary movements, and vision problems as well as cognitive or sensory impairment. Although the majority of patients with Moyamoya disease experience recurrent ischemic or hemorrhagic stroke, a subpopulation may also suffer from chronic hypoperfusion syndromes.
Moyamoya disease is a progressive cerebrovascular disorder that can be classified in 6 stages, each with typical angiographic findings, according to the Suzuki classification (106).
In addition to Moyamoya disease, Moyamoya-like vascular changes are seen in association with radiotherapy to the head or neck (particularly radiotherapy for optic gliomas, craniopharyngiomas, and pituitary tumors) as well as with other conditions that include Down syndrome, neurofibromatosis type 1 (with or without tumors of the hypothalamic-optic pathway), and sickle cell disease.
Medical therapy for Moyamoya disease includes single antiplatelet medication, the most often used is aspirin 81 to 325 mg daily for 5 to 10 days. Still, many patients will experience mental decline and multiple strokes because of the progressive narrowing of arteries. Therefore, cerebral blood-flow augmentation surgery is often performed. Options for cerebral revascularization include direct EC-IC bypass (eg, STA-MCA bypass) as well as indirect bypass techniques (eg, encephaloduroarteriosynangiosis, encephalo-myo-synangiosis, or omental transposition). Although many surgeons prefer direct bypass techniques in adult patients (to afford immediate improvement in cerebral hemodynamics), indirect methods remain popular, particularly in children and juvenile patients in whom they promote a robust extracranial-intracranial collateralization over a period of months to years.
Acute ischemic stroke. Intravenous thrombolysis using alteplase remains the first-line therapy for eligible patients with acute ischemic stroke, provided that treatment is initiated within 4.5 hours of clearly defined symptom onset. For the time being, eligible patients should receive intravenous alteplase without delay even if subsequent mechanical thrombectomy is being considered.
Indications and evidence. The purpose of mechanical thrombectomy is to restore cerebral blood flow for salvaging ischemic brain tissue that is not already infarcted. Mechanical thrombectomy is indicated for selected patients with acute ischemic stroke due to large artery occlusion regardless of whether they received intravenous thrombolysis for the same ischemic stroke event.
There was a turning point for mechanical thrombectomy in 2015 when 5 multicenter, open-label randomized controlled trials (MR CLEAN, ECAPE, SWIFT PRIME, EXTED-IA, and REVASCAT) unequivocally demonstrated that early intra-arterial treatment with second-generation mechanical thrombectomy devices in the early time windows (defined as 6 hours from last seen well) is superior (defined as significant difference in 90-day modified Rankin Scale score) to standard treatment with intravenous thrombolysis alone for ischemic stroke caused by a documented proximal anterior circulation artery occlusion (09; 16; 47; 64; 97). The number needed to treat for one additional person to achieve functional independence in these trials ranged from 3 to 7.5, and mechanical thrombectomy was beneficial across a wide range of patient subgroups including patients older than 80 years, patients with high initial stroke severity, and patients not receiving intravenous thrombolysis (48).
Mechanical thrombectomy has also been shown safe and effective in the later time windows (6 to 24 hours) and for “wake-up” stroke patients who have a clinical deficit that is disproportionally severe compared with the volume of infarction on advance imaging studies (for details, see DAWN and DEFUSE 3 trial eligibility criteria) (02; 82).
Finally, mechanical thrombectomy may be a reasonable treatment option for patients with acute large artery occlusion in the posterior circulation, such as the basilar artery, the vertebral artery, or the posterior cerebral artery occlusion. However, benefits of mechanical thrombectomy for posterior circulation large artery occlusions remain somewhat uncertain (88).
Technique. First-generation stent retrievers (“stentrievers”), such as the Merci Retriever or the Penumbra System® devices, may increase recanalization rates in selected patients, but their ability to improve functional outcome in patients with acute large artery occlusion remains unproven (102; 11; 12). Second-generation stentrievers, such as the Solitaire™ Flow Restoration Device and the Trevo® Retriever, achieve significantly higher reperfusion rates and better patient outcomes (83; 99). These second-generation devices were used in the positive thrombectomy trials, MR CLEAN, ECAPE, SWIFT PRIME, EXTED-IA, and REVASCAT (09; 16; 47; 64; 97). Catheter aspiration techniques, such as direct aspiration for thrombectomy (ADAPT), employ a catheter to aspirate the thrombus as the first approach. ADAPT has comparable rates of revascularization and functional outcome benefits as second-generation stentrievers (76; 69; 108).
The type of anesthesia used for mechanical thrombectomy may have some impact on short- and long-term outcomes, but given the inconsistency of currently available data, either conscious sedation or general anesthesia may be used, and the type of anesthesia is best chosen based on individual patient risk factors, surgeon preference, and institution experience (88). Blood pressure should be closely monitored and managed during mechanical thrombectomy. There is a consensus in the neurovascular community that the systolic blood pressure should be maintained in the 150 to 180 mmHg range prior to reperfusion and should be lowered below 140 mmHg once reperfusion has been achieved (47; 82; 88; 05).
Side effects and complications. Mechanical thrombectomy is not associated with increased rates of symptomatic intracranial hemorrhage or mortality. Reported complications include failure to achieve complete revascularization, new ischemic stroke in a different vascular territory (09), and access site hematoma and pseudoaneurysm formation (16; 47).
The technical advancement that made this possible was the introduction of "stentrievers," which are devices that can be deployed just like a self-expandable stent across the occluding particle but remain attached to a wire that allows the operator to pull them back into a guide catheter, thereby retrieving the embolic material.
These devices, now in their third generation of design, introduced elements of efficiency and speed to urgent revascularization (ie, rescue) and changed the landscape of the care of acute ischemic stroke. The impact of thrombectomy is supported by the remarkable consistency and reproducibility of the results of the different studies, several of which were stopped following interim analyses due to the loss of equipoise derived from the magnitude of benefit observed in their endovascular treatment arms. There are obvious differences and similarities in the design of these studies, yet the weight of their results has shaped our current approach to these patients. In addition, more recent publications have continued to confirm the data outlined in Table 3, including the HERMES metanalysis, which consolidated the experience derived from the 5 studies considered pivotal (98).
MRCLEAN | SWIFT PRIME | EXTEND-IA | ESCAPE | REVASCAT | HERMES | |
Population selection | ||||||
Patients (endo only) | 233 | 98 | 35 | 165 | 103 | 634 |
Stroke severity (NIHSS) | ≥ 2 | ≥ 8 & < 30 | None | > 5 | ≥ 6 | N/A |
Prescription interval (hours) | ≤ 6 | ≤ 6 | ≤ 6 | < 12 | 8 | |
Collaterals (ASPECTS) | No | No | No | ≥ 5 | ≥ 7 | |
Penumbra imaging | No | Yes | Yes | Yes (") | No | |
Pre-stroke function (mRS) | ≤ 2 | ≤ 1 | < 2 | ≤ 2 | ≤ 1 | |
Preceding intravenous-TPA | 203 (87.1%) | 98 (100%) | 35 (100%) | 120 (72.7%) | 70 (68%) | 526 (83%) |
Procedural metrics | ||||||
ETO – groin (min) (*) | 260 | 224 | 210 | 185 | 269 | 238 |
Groin – flow (min) (*) | NR | 28 | 38 | 56 | NR | 48 |
TICI 2b+3 | 115 (58.7%) | 73 (88%) | 25 (86%) | 113 (72.4%) | 67 (66%) | 390 (71%) |
Outcome metrics | ||||||
90-day MRS 0-2 (%) | 32.6 | 60 | 71 | 53 | 43.7 | |
Mortality | 27 (11.6) | 12 (12%) | 3 (9%) | 17 (10.4%) | 19 (18.4%) | 97 (15.3%) |
Infarct volume (ml) (*) | 49 | 32 | 105 | NR | 16.3 | NR |
Trial stopped early | No | Yes | Yes | Yes | Yes | N/A |
Safety metrics | ||||||
Remote embolism | 20 (8.6%) | NR | 2 (6%) | NR | 5 (4.9%) | NR |
Dissection | 4 (1.7%) | NR | NR | 1 (0.6%) | 4 (3.9%) | NR |
Wire perforation | 2 (0.9%) | NR | 1 (2.8%) | 1 (0.6%) | 5 (4.9%) | NR |
Totals hemorrhages | NR | 9 (9.1%) | NR | NR | 29 (28%) | NR |
Sx hemorrhages | 18 (7.7%) | 0 (0%) | 0 (0%) | 6 (3.5%) | 7 (6.7%) | 28 (4.4%) |
HI1 | 1 (0.4%) | NR | NR | 27 (16.4%) | NR | NR |
HI2 | 1 (0.4%) | NR | NR | 25 (15.2%) | NR | NR |
PH1 | 0 (0%) | 4 (4%) | 4 (11%) | 5 (3%) | NR | NR |
PH2 | 14 (6.0%) | 1 (1%) | NR | 4 (2.4%) | NR | 32 (5.1%) |
SAH | 2 (0.9%) | 4 (4%) | NR | 5 (3%) | 5 (4.8%) | NR |
|
The shift from a strict "therapeutic time window" to a more individualized approach obeys the successful introduction of imaging techniques capable of identifying potentially salvageable (ie, ischemic but not infarcted, or "ischemic penumbra") brain tissue along the time continuum (Liu et al 2010; 04). Data from the studies that included CT or MR perfusion as intrinsic steps in their protocols (ie, SWIFT PRIME and EXTEND-IA) demonstrated that certain imaging patterns are associated with a greater chance of improvement following thrombectomy or to predict futility of intervention (16; 97; 77).
Multiple trials, such as MR CLEAN, ECAPE, SWIFT PRIME, EXTED-IA, and REVASCAT, demonstrated the superiority of mechanical thrombectomy over intravenous thrombectomy alone among patients with acute stroke when performed within 6 hours of symptom onset (09; 16; 47; 64; 97). Even if benefits of the intervention decline as the time since onset increases, there remains a subset of patients in whom ischemic brain tissue remains salvageable in case reperfusion. Herein, the DAWN and DEFUSE 3 trials demonstrated a 90-day functional outcome benefit of mechanical thrombectomy over standard therapy alone in patients with anterior circulation large artery occlusion and favorable perfusion imaging pattern in the 6- to 24-hour window after initial onset of symptoms (02; 03; 82).
The "ideal" imaging profile of a patient who is likely to benefit from thrombectomy for large artery occlusion is one with: (a) a much larger area of penumbra than ischemic "core" (ie, large mismatch), (b) a small area of ischemic "core," and (c) normal cerebral blood volume. The specifics of how this has translated in the clinical trials are displayed in Table 4.
Study | Core threshold | Core volume | Penumbra threshold | Penumbra volume | Mismatch ratio | Mismatch volume |
SWIFT PRIME | NS | < 50 ml < 80 y | Tmax > 10 sec | ≥ 15 ml | > 1.8 | NS |
< 20 ml ≥ 80 y | ||||||
EXTEND-IA | < 30% | < 70 ml | Tmax > 6 sec | NS | > 1.2 | > 10 ml |
The purpose of revascularization procedures is to reduce the risk of subsequent stroke by restoring or improving cerebral blood flow. Although there are published guidelines relevant to each topic, these guidelines may not be strictly applicable to every clinical scenario.
Extracranial circulation. Guidelines recommend that patients who have experienced a transient ischemic attack or nondisabling stroke caused by severe extracranial carotid stenosis (ie, 70% to 99% by angiography) should be considered for revascularization, either by carotid endarterectomy or carotid artery stenting, provided the procedure is carried out with less than 6% risk of stroke, myocardial infarction, and death. Patients with moderate degree of stenosis (ie, 50% to 69% by angiography) should be also considered for revascularization, depending on individual patient factors, such as age and comorbid conditions. In addition, it is recommended that revascularization is carried out within 2 weeks of the index event. In choosing between carotid endarterectomy and carotid artery stenting, the guidelines suggest a preference for carotid endarterectomy in older patients (ie, over 70 years of age) and a preference for carotid artery stenting in high-surgical-risk patients or those with nonatherosclerotic lesions. Finally, asymptomatic patients with more than 70% carotid stenosis by angiography should be considered for revascularization, either by carotid endarterectomy or by carotid artery stenting, provided the procedure is carried out with less than 3% risk of stroke, myocardial infarction, and death (65).
The guidelines also recommend that patients with transient ischemic attack or nondisabling strokes caused by severe extracranial vertebral stenosis (ie, 70% to 99% by angiography) be considered for revascularization by stenting or open surgical procedures (eg, endarterectomy) if symptoms persists or recur despite maximal medical therapy, provided the procedure is carried out with less than 6% risk of stroke, myocardial infarction, and death (65).
Intracranial atherosclerosis. Guidelines recommend medical therapy using antiplatelet agents (single or in combination), statins, and blood pressure control as first-line treatment for patients with transient ischemic attack or nondisabling stroke caused by intracranial atherosclerosis (65). The use of percutaneous transluminal angioplasty or stenting in patients with intracranial stenosis is not recommended as initial treatment and is considered investigational in all other settings.
Cerebral bypass. According to the guidelines, EC-IC bypass remains investigational for patients with recurrent or progressive ischemic symptoms ipsilateral to a stenosis or occlusion of a surgically inaccessible carotid artery (65). EC-IC bypass is not recommended for patients with transient ischemic attack or nondisabling stroke due to stenosis or occlusion of the carotid or middle cerebral artery. Finally, the guidelines do not address the application of EC-IC bypass for the treatment of Moyamoya disease, its role in the adjuvant management of complex skull base tumors requiring sacrifice of a large intracranial artery, or its potential use for the treatment of complex intracranial aneurysms requiring trapping and distal revascularization.
Acute ischemic stroke. Guidelines recommend the use of thrombectomy in addition to (not instead of) the use of intravenous thrombolysis in eligible patients (87). Eligibility factors include acute large anterior circulation artery occlusion, pre-stroke mRS <2, age = 18 years or older, NIHSS = 6 or greater, ASPECTS = 6 or greater, and groin puncture within 6 hours of estimated time of onset and in up to 24 hours in select patients (63; 87).
As noted above, there are scenarios in which each of these procedures is not recommended, primarily because of the perceived unfavorable benefit-to-risk ratio. However, it is important to consider the uniqueness of each patient's circumstances while also considering the natural history of the pathology being treated.
The most important potential complications from all revascularization techniques include: (A) ischemic stroke, typically from arterial closure or downstream embolization; (B) intracerebral or subarachnoid hemorrhage, typically from reperfusion injury or arterial perforation during the procedure; (C) myocardial infarction, as a general surgical complication; and (D) death, caused by any of these. The rates of acceptable complications for the various procedures have been described above, together with their potential, allowing assessment of the benefit-to-risk ratio. The latter, however, must always be assessed in the context of each patient's comorbid status and overall severity score.
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Daniel Zumofen
Dr. Zumofen of Maimonides Medical Center has no relevant financial relationships to disclose.
See ProfileSteven R Levine MD
Dr. Levine of the SUNY Health Science Center at Brooklyn has no relevant financial relationships to disclose.
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