- Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, California, USA
- Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California, USA
- Neurovascular Imaging Research Core, David Geffen School of Medicine, University of California, Los Angeles, California, USA
- Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, California, USA
- Department of Emergency Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA
Correspondence Address:
James I. Ausman
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, California, USA
Department of Emergency Medicine, David Geffen School of Medicine, University of California, Los Angeles, California, USA
DOI:10.4103/sni.sni_373_17
Copyright: © 2018 Surgical Neurology International This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.How to cite this article: James I. Ausman, David S. Liebeskind, Nestor Gonzalez, Jeffrey Saver, Neil Martin, J. Pablo Villablanca, Paul Vespa, Gary Duckwiler, Reza Jahan, Tianyi Niu, Noriko Salamon, Bryan Yoo, Satoshi Tateshima, Manuel M. Buitrago Blanco, Sidney Starkman. A review of the diagnosis and management of vertebral basilar (posterior) circulation disease. 24-May-2018;9:106
How to cite this URL: James I. Ausman, David S. Liebeskind, Nestor Gonzalez, Jeffrey Saver, Neil Martin, J. Pablo Villablanca, Paul Vespa, Gary Duckwiler, Reza Jahan, Tianyi Niu, Noriko Salamon, Bryan Yoo, Satoshi Tateshima, Manuel M. Buitrago Blanco, Sidney Starkman. A review of the diagnosis and management of vertebral basilar (posterior) circulation disease. 24-May-2018;9:106. Available from: http://surgicalneurologyint.com/surgicalint-articles/a-review-of-the-diagnosis-and-management-of-vertebral-basilar-posterior-circulation-disease/
Abstract
We have reviewed the English literature published in the last 70 years on Diseases of the Vertebral Basilar Circulation, or Posterior Circulation Disease (PCD). We have found that errors have been made in the conduct and interpretation of these studies that have led to incorrect approaches to the management of PCD. Because of the difficulty in evaluating the PC, the management of PCD has been incorrectly applied from anterior circulation disease (ACD) experience to PCD. PCD is a common form of stroke affecting 20-40% patients with stroke. Yet, the evidence is strong that the Anterior Circulation (AC) and Posterior Circulations (PC) differ in their pathology, in their clinical presentations, in the rapidity of development of symptoms, in optimal imaging methods, and in available treatments.
Keywords: Posterior circulation, stroke, vertebral basilar insufficiency
OPENING STATEMENT
A number of previous reviews of vertebral basilar circulation or posterior circulation disease have been written over the past 35 years[
INTRODUCTION - SHORT SUMMARY OF THIS PAPER FOR THE READER, WITH KEY REFERENCES
Because the anatomical location of the vertebral basilar vessels is not easily accessible for pathological, imaging, clinical, or management studies, it has taken 70 years of publications to begin to understand the differences between the PCD and ACD.
Key studies by decade relating the AC to the PC and PCD
Postmortem anatomical studies have shown that 65% of the brains studied have an incomplete Circle of Willis with up to 50% with absent or hypoplastic posterior communicating arteries. Thus, the anatomical connection between the AC and PC is impaired in half of the patients presenting with PCD.[
The seminal paper by Kubik and Adams in 1946[
In the 1980s, the introduction of new detailed subtraction angiography showed the anterior and posterior circulations better than any known imaging modality at that time. With the addition of digital subtraction, four-vessel angiography became, and still is, the “gold standard” for evaluating AC and PC disease.[
The publication of the first randomized surgical trial of the best medical vs EC–IC bypass surgical treatments was published as the EC–IC bypass trial in 1985. EC–IC bypass was not found of value in the treatment of ACD.[
Computed tomography (CT) and magnetic resonance (MR) imaging and angiography was introduced in the 1980s and 1990s and used as a basis of clinical trials of various medcial therapies, even though the imaging studies were not able to demonstrate PC lesions with high accuracy, calling into question the conclusions of these studies.[
In the first decade of the 2000s, 60 years after the first clinical pathological study of PCD, Caplan et al. developed a large registry of 407 patients with PCD who were evaluated angiographically and followed clinically. Accrual of patients in this study preceded IVtPA and acute interventional approaches to treatment. Many patients were entered days after onset. Yet, as thorough as this registry was, it represented an eclectic sample of the universe of patients with PCD seen during the 1980–1996 period, as the authors admit. Only three patients had surgery and five interventional treatment, indicating a further treatment bias of the study. There were no patients described who were refractory to medical therapy as in the surgical studies.[
Although intravenous thrombolytic therapy was used in patients with PCD, most studies reported a mixture of patients with ACD and PCD. Two studies on non-angiogrammed patients with PCD reported favorable results after IVtPA.[
It was not until the 2010 decade that significant advances in the diagnosis and treatment of PCD were reported. (1) There were reports of the successful use of stent retrieval systems to remove a basilar artery thrombosis, a subset of the universe of PCD.[
(2) Using QMRA, Charbel et al. were able to differentiate patients with symptomatic PCD with low posterior circulation blood flows from those with normal flows to reveal another subset of patients with PCD. Those with normal flows had a much higher stroke-free survival than those with low PC flows. This latter category of patients was amenable to reconstructive PC techniques and then resumed a postoperative stroke-free course that paralleled those who had normal PC flows.[
(3) In a third major advance since 2010, studies using 7T MR angiography were able to delineate the PCD in far better detail than angiography. This imaging modality available in limited centers represents another diagnostic method of evaluation with QMRA.[
(4) Finally, in a large population study from Oxford England, Paul et al.[
In an observation from a human surgical study, when both ends of the basilar artery were occluded, and the basilar artery incised to remove an atherosclerotic plaque, blood was seen coming into the basilar artery from the paramedian vessels indicating that there was collateral circulation in the brainstem in vessels formerly believed to be end arteries. This observation explains the reason for the survival of patients with BAO with minimal deficits.
Lastly, after a review of the conclusions from the voluminous studies over the 70-year period by decade, indicating the distinct differences between the AC and PC in pathology, clinical presentations, imaging, and management strategies, it is obvious that these reports came from separate subset samples of the universe of patients with PCD and are not generalizable, making most of the literature on PCD difficult to assess and use in analyzing treatment of PCD. Yet, this conclusion is important in that it suggests along with the other studies cited, that PCD is composed of a number of different subsets of pathology that will require individual types of treatments first described by Caplan in 1975.[
EPIDEMIOLOGY
Diseases of the vertebral basilar circulation (VBC) represent 20–40% of all the strokes in a year.[
Anatomy of the circle of Willis and brainstem
Sixty-five percent of the people have abnormalities or anomalies in their Circle of Willis and 18–32% have one hypoplastic and 24–49% have bilateral hypoplastic posterior communicating arteries.[
Observation #1: Two-thirds (66%) of the population have variations in their circle of Willis that can affect the collateral circulation between the AC and the PC
SPECIFIC BRAINSTEM VASCULAR SYNDROMES
This review will not cover the specific syndromes of vascular occlusion of the basilar artery branches that has been reviewed in other publications.[
CHRONOLOGICAL REVIEW OF PCD LITERATURE
1940s
Basilar artery thrombosis
While there was literature on the vascular syndromes of the brainstem reported previously, the symptoms of basilar artery thrombosis had not been established. In 1946, Kubik and Adams reported a detailed clinical and autopsy study of 18 patients with basilar artery thrombosis.[
The brainstem and cerebral symptoms and signs in all cases of basilar thrombosis were progressive over days to include a combination of motor sensory loss of the face and 1–4 extremities, cranial nerve dysfunction, dysarthria, cerebellar signs, nystagmus, and incontinence.[
There were 7 cases of embolism to the basilar artery all of whom presented with sudden or rapidly progressing coma. One had a rare tumor embolus to the basilar artery, 3 others had a cardiac murmur, and 2 had atrial fibrillation. in these patients, death occurred in 2–35 days.[
Forty-six years later, in 1990, Morgan et al. reported a case of rapidly progressing basilar artery thrombosis with a deteriorating level of consciousness dysarthria, dysphagia, and periods of apnea. Angiography demonstrated an occluded basilar artery, patent vertebral arteries, with collateral filling of the basilar tip but no posterior communicating vessels. The patient was treated with intra-arterial thrombolytic agents given directly at the site of occlusion to lyse the clot and restore the patient to a normal clinical state. An atheroma at the mid basilar artery was found and a superficial temporal artery (STA) to superior cerebellar artery (SCA) bypass was performed insuring the competency of the distal basilar artery circulation. The patient recovered. This report provides an example of what can be done in the 21st century for this dreaded disease with rapid diagnosis and treatment.[
1950s
Early reports on diagnosis and treatment of PCD
In 1955 Millikan and Siekert performed a less detailed study of patients with basilar artery occlusion. Seventy percent of Millikan and Siekert's patients developed symptoms before occlusion. Early in the course of the disease, the symptoms and signs were difficult to localize to the brainstem and alone were “non-specific,” but as the course of the disease progressed the involvement of the basilar artery became apparent. In many cases, the early symptoms and signs were transitory leading them to describe the syndrome as “intermittent insufficiency of the basilar arterial system,” or as is commonly used, vertebral basilar insufficiency (VBI).[
Seeing laminations in the basilar thrombus, they believed that the occlusion occurred progressively and started Coumadin therapy empirically to stop that progression, which appeared successful in their initial 10 patients.[
Early angiography
Direct vertebral angiography by vertebral artery puncture of the vertebral basilar system was introduced in 1949 but had a risk of 25%, which made it impractical for clinical use.[
Observation #2: Diagnostic angiography for PC disease is more difficult to perform than for AC disease. Medical Treatment of PCD was extrapolated from studies of ACD
Anatomical divisions of the vertebral artery
To understand the pathology reports and subsequent studies on the VBC, it is important to review the anatomical vertebral artery segments. Numerous investigators have divided the vertebral artery into four segments.[
1960s
Pathology of the VB system
Because of the lack of information on the pathological changes from the vertebral origin to the intracranial VBC, papers were published in the late 1950s and early 1960s on this subject. This information provided a basis for understanding the pathological changes in the VBC.
The pathology studies examined the entire extra and intracranial vertebral basilar circulation.[
The fundamental conclusions that can be made by mixing the data from these studies are:
Atherosclerotic disease occurs throughout the vertebral artery[ Atheromas are localized at the vertebral origin, the mid vertebral artery, C3, the proximal basilar and the posterior cerebral arteries with the highest percentage at the vertebral artery origin[ Since the vertebral arteries are smaller than the carotids, plaques produce more stenosis in the vertebrals than in the carotids[ Vertebral plaques are less ulcerated than in the carotid arteries[ Most occlusions in the VBS occur at the vertebral artery origins or near or at the sites of stenosis[ The atheromas in the vertebral develop a thrombus that can embolize[ The right vertebral has more stenotic lesions (75%) than the left vertebral[ Distal V3 lesions are more symptomatic than proximal V1 stenoses[ Atheromas occur more in the proximal than distal basilar artery[ Atheromas can produce flow related symptoms in studies done with clinicopathological correlations[ Occlusion of one vertebral artery does not assure adequate circulation to the VBC[ Dissections can occur at the vertebral origins, in the mid-vertebral, C3, and basilar sites[ Atherosclerosis is the cause of basilar occlusion 94% of the time[ Atherosclerotic occlusions of the posterior cerebral arteries in a small series of 16 patients occurred in 63% of the cases; antegrade thrombus produces occlusion in 5/16 (31%) and cardiac embolus occluded the posterior cerebral arteries 1/16 cases (6%); 1/3 (33%) of posterior cerebral artery occlusions were bilateral[ In some patients over 75 years with PCD, there were no lesions in the VBC[ The total cerebral circulation is important to understand in evaluating the adequacy of perfusion in the VBC[ Narrowing of one of the four carotid or vertebral vessels means a high probability of narrowing in others[ More recent studies by Caplan et al.[
Observation #3: Studies of the pathology of atherosclerosis in the VBC establish significant differences in the types of and locations of cerebrovascular pathology between the PC and the AC
While these pathology studies were being reported, some important information was emerging that suggested that hemodynamic and blood follow changes can account for symptoms in the VBC.
Subclavian steal
In 1961, Reivich et al. reported the first cases of subclavian steal syndrome (SSS), an excellent example of the flow-related (hemodynamic) production of symptoms in the posterior circulation.[
In a laudatory editorial on the Reivich et al. report of SSS in the NEJM, Fisher reported that transient spells of cerebral ischemia had been noted in clinical pathological reports in the past 10 years but not understood.[
Studies were performed in four dogs with both carotids and vertebrals exposed and flows recorded extravascularly. With occlusion of the left subclavian artery there was a reversal of flow in the left vertebral artery that almost equaled its antegrade flow before occlusion. Right vertebral flow increased by 78% as did flow in each common carotid artery by 22% and 23%. The calculated reduction in total cerebral blood flow flow was 41%.[
Observation #4: The discovery of the subclavian steal syndrome, with a stenosis or occlusion in a vessel far removed from the brain but yet producing vertebral basilar symptoms described by numerous clinical and pathology investigators previously, establishes flow deficits in the AC and PC as a cause of vertebral basilar vascular symptoms and signs in PCD[
1970s
Multi-institutional angiographic study to determine efficacy of surgery in accessible lesions of the carotid and vertebral arteries
By the 1970s, disease of the VBC was known clinically and pathologically but could not be definitively diagnosed angiographically. There were no surgical treatments for disease beyond the origins of the vertebral arteries. Angiography had become safer and more widely used.[
Other important studies at the time
Others[
Caplan et al. stated[
The medical treatment of cerebrovascular disease was summarized by Byer and Easton. Heparin and Coumadin were used for progressing stroke while Aspirin was useful for AC disease, but there seemed to be little further to offer the patients with PCD.[
1980s
Reconstructive surgery for PCD
With the development of microvascular surgery and small vessel anastomosis by Yasargil in the late 1970s,[
Neurosurgeons studied the vertebral basilar circulation from the vertebral origins to the basilar artery and its terminal branches including the posterior communicating arteries with detailed angiography and subtraction views to understand the anatomy of the obstructive lesions and plan for reconstructive vascular surgery. There are three groups who have had extensive experience with the surgical treatment of PCD, (Ausman et al.,[
The revascularization procedures used by these investigators for the extracranial vertebral artery included vertebral to carotid transpositions, which appeared a safer procedure than removal of the vertebral origin plaque itself.[
Vertebral artery surgery
The 1980s marked the introduction of surgery on the vertebral origins[
Surgery for intracranial arterial disease of the PC
Using various EC–IC bypasses to the PC, Hopkins et al. in their initial report of 45 cases found a 2% mortality, 0 morbidity, and 0 strokes after PC vascular reconstruction of the intracranial vessels.[
Furthermore, Ausman et al.[
Observation #5: These surgical studies showed that diseases of the PC from the vertebral origin to the intracranial vessels could be successfully treated surgically in a selected sample of patients with PCD who had failed medical management
International EC–IC Bypass Study
As EC–IC bypass surgery became more common with successful reports in individual case studies or series for relieving symptoms of cerebral ischemia, it became important to develop a RCT of this surgery. The first RCT of a surgical therapy (EC-IC Bypass Study) versus best medical therapy for TIAs in the anterior circulation in patients with carotid occlusion was published in 1985.[
A second EC–IC bypass study was performed[
Observation #6 Although PCD was not studied in either EC–IC bypass study, the conclusion was made that EC–IC bypass surgery for PCD was of no value as a treatment for PCD without any supporting scientific evidence from the studies performed
Results of medical and surgical management of patients with PCD refractory to maximal medical therapy similar to the surgically treated cases
There was very little information on the medical management of patients similar to those treated surgically. Likely, those who failed medical therapy, died, or developed an infract, but these patients are not reported. Jones et al. reported that in 37 consecutive non-angiogrammed patients with infarcts from PCD, there was a 27% mortality, 2.5-times higher than in carotid artery system disease.[
In a study closest to the surgical populations reported above, Moufarrij et al. examined 44 patients with >50% stenosis of the distal vertebral or basilar artery presenting with VB-TIA or infarction who were followed for 6.1 years.[
Observation #7: Still there is no published comparable medical study of patients who failed maximal medical therapy to the surgically treated group of patients of patients with PCD who had failed maximal medical treatment
The goal of treatment for any disease is to provide the treatment with the lowest risk and the best outcome at each stage of the disease. No treatment is also therapeutic option. That option also has risks and must be compared with the risks and benefits of other options available. Vascular reconstruction for PCD is a treatment option that has been inappropriately disregarded because neurologists and neurosurgeons worldwide accepted inaccurately analyzed data, and the investigators of those studies supported financially by the US Government have not admitted the failures and limitations of their research.[
From 1985 until 2011, surgery for PCD was not considered in the treatment of these patients. In the Stroke Guidelines of the American Heart Association and American Stroke Association of 2011, “for those patients with 50–99% stenosis of a major intracranial vessel EC–IC bypass surgery was not recommended.” However, “for those with extracranial vertebral stenosis, surgery or endovascular treatment “should be considered for patients having symptoms despite optimal medical management.”[
Observation #8: Yet, in a critical analysis of the data in the literature on PCD over decades, there is excellent evidence, in critically ill patients, who had failed medical therapy, that the outcomes of surgery were superior to no therapy or medical therapy, which would have had a high mortality rate
1990s
Imaging diagnosis of PCD
Starting in the mid-1990s minimally invasive diagnostic methods were employed that included CT angiography and/or MR angiography as a replacement for intra-arterial digital angiography as screening and diagnostic tests.[
MR angiography has been used by many investigators as a noninvasive, negligible risk, alternative to IA angiography in most studies from the late 1990s forward.[
Observation #9: As found 40 years ago, imaging of PCD is far more difficult to perform and interpret than ACD. IA angiography is still the gold standard for the diagnosis of PCD, although it is more difficult to perform technically according to angiographic radiologists. MRA and CTA can only be regarded as screening examinations because the limit of their resolution is less than that of IA angiography. For those with symptoms and signs of PCD and with normal MRA and CTA, IA angiography should be performed. Had neurologists developed the capability to perform cerebral angiography as cardiologists did for cardiac disease, neurologists would have not been reluctant to investigate the vascular anatomy of the brain. This specialty change would have propelled a more rapid understanding of the ACD and PCD
2000–2010
NEMC-PCR
Caplan et al. stated, “Autopsy studies select patients who die of stroke or its complications. Angiographic studies also contain selection bias since more severely ill patients have been studied. Unfortunately, no detailed reports from large registries of posterior circulation ischemia patients define the frequency and location of vascular occlusive lesions using modern vascular imaging techniques.”[
Inclusion criteria were that:
All 409 patients were examined by Drs. Caplan, Pessin or DeWitt, Patients must have had posterior circulation TIAs or strokes within the past 6 months. Stroke patients must have had CT or MRI documented infarction. TIAs had to be clearly vertebrobasilar and brain imaging and vascular tests must have shown vertebrobasilar territory infarction or occlusive lesions, and Investigations must have been adequate.[
By the inclusion criteria stated above this sample of patients represents a defined subset of the PCD population.
The sample of the universe of patients with PCD in their Registry, included 63% males, 37% females, with an average age of 60 years; 84% were white, 9.5% Asian, 4% Black, and 2% Hispanic.[
Embolism was the likeliest stroke mechanism for 40% of their cases, Cardiac embolism in 24%, artery to artery in 14%[
The distribution of lesions was among their defined proximal, middle, and distal VB territories and was mixed with the predominant territory being distal, consistent with the predominance of embolic causes of PCD in their sample. (”The distal territory included regions supplied by the rostral BA, SCA, PCA and their penetrating artery branches-midbrain, thalamus, SCA cerebellum, and PCA territories.”)[
The 30-day mortality of the NEMC-PCR was “very low,” at 3.6%. Twenty-one percent of patients in their series had died by 30 days or had a major disability, while almost 80% recovered with little or no disability.[
Highlights from the authors' second paper in the discussion of the 407 patients in the NEMC-PCR[
“…Intracranial occlusive lesions are most common in blacks, individuals of Asian origins, and women… …necropsy studies showed that although extracranial vertebral artery lesions (ECVA) were common, most posterior circulation infarcts were attributable to intracranial occlusive disease …Subclavian artery disease patients often have coexistent ICA disease that is usually responsible for brain ischemia … The benignity of atherosclerotic vertebral artery origin (VAO) lesions was attributed to: (1) the capacity to develop collateral reconstitution of the ECVAs; (2) the usual presence of two viable arteries that join together intracranially, so that if one became compromised, the contralateral artery could compensate adequately; and (3) the slow development of luminal compromise by atherosclerotic plaques allowing time for collateral development…Infarcts in patients with VAO disease were mostly attributable to artery-to-artery embolism arising from the ECVA …Hypoperfusion related to VAO occlusive lesions was usually transient causing brief spells of dizziness, veering, visual blurring, and ataxia. Attacks were self-limited probably reflecting reconstitution of the ECVA distal to the occlusion …The closer an artery is to the brain, the more likely that occlusion will lead to brain infarction …The patients with severe multifocal disease most often had benign courses usually characterized by multiple TIAs but few serious strokes …[in basilar artery disease] Some had headache and episodic TIAs during the weeks preceding an acute stroke “…The case mix of our patients with BA disease likely included more patients with less severe ischemia than in other reports…We evaluated more patients with minor posterior circulation ischemia using presently available noninvasive vascular and brain imaging than was possible in the past. Undoubtedly, this imaging led to discovery of BA disease in many patients who would likely have not been exposed to catheter angiography in the past so that BA disease would have been missed…” …The pathology within penetrating arteries consists of lipohyalinotic disruption of the arterial lumen.”
“This report documents the frequent coexistence of multiple arterial constrictive lesions, most often involving the ICVAs bilaterally, often with accompanying BA and ECVA stenosis. Prior reports contain hints of this group of patients although none describes this group in detail.[
Population studies
Marquardt et al. in their population study of 2009 from Oxford, England in patients with VBI imaged with 1.5 T MR angiography, found that there was a 45% risk of recurrent stroke in 90 days from presentation.[
Observation #10: The extensive studies by Caplan et al., of the NEMC-PCR population of patients,[
2000–2017
Randomized drug trials, IVtPA, and interventional approaches to PCD and basilar artery occlusion
Randomized drug trials
From 2000, there were a number of drug treatment studies performed using CT angiography and MR angiography to evaluate CVD. These studies were devoted principally anterior circulation disease[
Observation #11: These drug studies cannot be used as definitive guides to medical therapy for PCD, specifically. Also, it is clear that many of the patients had not been on maximal medical therapy prior to enrollment and so they cannot be compared to the surgical series in which patients had become unresponsive to medical management
Intravenous tPA
In 2005[
In 2011 Report of the Specialty Societies on “Guideline on the Management of Patients With Extracranial Carotid and Vertebral Artery Disease: Executive Summary,”[
In 2011, Sarikaya et al. reported that “no randomized controlled trial or Phase IV study investigated the safety and efficacy of IVT according to stroke territory and that “just 5% of patients from the National Institutes of Neurological Diseases and Stroke (NINDS) study had PCD, although approximately 20% to 25% of all ischemic strokes are localized in the posterior circulation.”[
Lindley et al. used Aleptase (tPA) for acute ischemic stroke in the IST-3 trial and randomized 3035 patients with ACD and PCD to receive IVtPA. Only 246 patients were in the PCD category and 110 were treated with IVtPA. The authors concluded that “Among the types of patient in the Third International Stroke Trial, this secondary analysis did not identify any subgroups for whom treatment should be avoided.”[
Observation #12: The evidence of the value of IVtPA for posterior circulation ischemia has been explored in limited studies and seemed to be of benefit in patient populations of PCS that were clinically but not angiographically defined. Results from the studies suggest that there is no harm to give iVtPA to patients with PCS, but no RCTs of IVtPA were reported. Given the evidence that symptoms may develop into a stroke quickly,[
Interventional treatments
At the beginning of the first decade of the 21st century there were numerous reports suggesting the promise of interventional treatments for PCD.[
From 2008–2014, major advances in removal of clots in large vessels of the anterior circulation were made. Badhiwala et al. summarized the results of “8 trials involving 2423 patients…including 1313 who underwent endovascular thrombectomy and 1110 who received standard medical care with tPA.” In general, “among patients with acute ischemic stroke, endovascular therapy with mechanical thrombectomy vs. standard medical care with tPA was associated with improved functional outcomes and higher rates of angiographic revascularization, but no significant difference in symptomatic intracranial hemorrhage or all-cause mortality at 90 days.”[
New advances in the treatment of basilar artery occlusion
Basilar artery occlusion (BAO) was first described by Kubik and Adams in 1946.[
What the authors of this study failed to recognize is obvious from the surgical bypass studies on patients who failed medical therapy described previously.[
Since that study, there have been other reports on successful reopening of the basilar artery or posterior cerebral arteries by endovascular thrombectomy and other treatments.[
Another study reported in 2016 by Fahed et al.,[
Observation #13: So far, interventional treatments for PCD have only been successful in the removal of acute basilar artery thrombosis
2010-2017 – Recent advances in the diagnosis and treatment of PCD
Natural history of PCD-2000–2017
From the late 1990s to 2017, numerous papers reported on the natural history of subsets of patients with PCD. As expected the results vary considerably reflecting the samples taken from the universe of patients with PCD.[
Given the tendency of Registries to produce selected samples of the universe of patients with PCD, there was a need for population based studies to give a more comprehensive view of patients with PCD.
Population Studies-Comparison of PC and AC of PCD
In 2009, Marquardt et al. collected patients with VBI from a population of 91,000 around the city of Oxford, England.[
Multiple TIAs with stroke were higher with VBS than with CS, and those with VBS >50%, had a high early recurrent TIA and Stroke rate of 46% in 90 days after presentation. Others note a recurrence rate of 10–15% per year.[
Observation #14: It appears that not only does the PC differ pathologically from the AC, but the diagnosis of its abnormalities is more difficult, interventional treatments are not successful with the exception of BAO, while surgery for those who fail medical management remains as a successful alternative that has been ignored. In addition, the clinical presentation of PCD symptoms is higher and develops faster into a stroke than of ACD stenosis
Thus, by 2010, after 70 years of studying PCD, we have multiple papers analyzing subsets of a universe of patients with PCD, which all have different natural histories evaluated by different methodologies. Regardless of all of this information about posterior circulation disease, about which far less is known that that of the anterior circulation,[
Quantitative measurement of flow in the posterior cerebral circulation and its relation to symptoms of PCD
Charbel et al. published several studies showing a highly accurate estimate of the blood flow in large and small cerebral vessels including the posterior circulation.[
A pilot study of management was performed to determine if a sample of symptomatic patients with VBD can be selected for different treatment options based on QMRA evaluations of cerebral blood flow.[
In a subsequent multi-institutional blinded RCT of medical management only,[
Observation #15: This RCT provides data on the natural history of a selected group of patients with VBI evaluated with QMRA. The results show that those with low flows in the PC have a significantly higher risk of stroke than those with normal flows.
A recent publication from the same group indicates that the blood flow in cerebral vessels decreases with age adding another factor to the anatomical variants in the Circle of Willis, and the pathological changes that develop in these vessels that can contribute to PCD.[
On the contrary, Savitz and Caplan “in the NEMC-PCR, 13 of 407 (3%) patients had hemodynamically sensitive ischemia, most commonly caused by bilateral intra-cranial vertebral-artery occlusive disease, and they had multiple brief episodes of dizziness, veering, perioral paresthesias, and diplopia.”[
Observation #16: Thus, a diagnostic test now exists that can help select patients for medical or surgical treatments for PCD
Early symptoms to recognize PCD
Throughout the 70 years, which this review covers, many studies have reported that patients with PCD can present with symptoms that do not fit the classic pattern of symptoms or signs involving the brain stem. Recent studies show that vertigo or hearing loss alone can be early symptoms of PCD.[
Paul et al. from the Oxford group prospectively studied a series of 275 patients from a population based group with vertebral basilar territory stroke to learn the symptoms they had 90 days preceding their stroke.[
Those symptoms included (1) isolated vertigo, (2) vertigo with nonfocal symptoms, (3) isolated double vision, (4) transient generalized weakness, (5) binocular visual disturbance as transient neurological attacks (TNA) in the vertebrobasilar territory. They also compared this population with 759 patients with carotid territory strokes. “Of all, 59 TNAs preceded (median 4 days, range: 1–90 days) vertebrobasilar stroke, only five (8%) fulfilled the National Institute of Neurological Disorders and Stroke (NINDS) criteria for PC TIA. The other 54 cases were isolated vertigo (n = 23), non-NINDS binocular visual disturbance (n = 9), vertigo with other non-focal symptoms (n = 10), isolated slurred speech, hemisensory tingling, or diplopia (n = 8), and non-focal events (n = 4). Only 10 (22%) of the 45 patients with isolated brainstem TNAs sought medical attention before the stroke and a vascular cause was suspected by their physician in only one of these cases.
Some reported symptoms as long as days, weeks, months, and years before their infarct and that their symptoms gradually progressed into PCD.[
Savitz and Caplan found less than 1% of their patients in the NEMC-PCD Registry had only one presenting symptom or sign[
Observation #17: These observations of the early appearance of the pre-VBS symptoms are troubling and mean that PCD symptoms can occur singly and very early in the presentation of PCD. Neurologists need to see these patients early to prevent PCD. Education of emergency room physicians and neurologists about the early symptoms of PCD is important to implement prevention of PCD stroke. Again, a significant difference was found between the AC and the PCD in the variable types of presenting symptoms and the rapidity of onset of stroke in the VBC compared with the AC
NEW IDEAS IN THE FUTURE FOR PCD
New ideas and personal observations-7T MR Angiography
In another study published in 2014 in Japan, Sato et al.[
Collateral circulation to the brainstem
In unpublished observations on direct surgery in a patient with an atheroma of the basilar artery, Ausman and his colleagues in unpublished observations found on isolating the diseased basilar artery with temporary clips, that upon removal of the atheroma, blood flowed from the small perforators from the brainstem into the endarterectomized basilar artery. This observation is the opposite of what we have been taught for decades that the perforators off the basilar artery are end arteries. From this observation in a live patient, that conclusion is incorrect. The observation explains why people with extensive occlusion of the basilar artery can survive with minimal or no symptoms because of the collateral circulation through and around the brain stem. Detailed cerebral angiography and even 7T MRA will become necessary standard to evaluate patients with PCD.
Arterial spin labelling in neuroimaging for blood flow determination
“Arterial spin labeling (ASL) is a magnetic resonance imaging technique for measuring tissue perfusion using a freely diffusible intrinsic tracer. As compared with other perfusion techniques, ASL offers several advantages and is now available for routine clinical practice in many institutions. Its noninvasive nature and ability to quantitatively measure tissue perfusion make ASL ideal for research and clinical studies. Recent technical advances have increased its sensitivity and also extended its potential applications.”[
Intracranial vertebral endarterectomy
In another study, Uschold et al. performed an endarterectomy of the vertebral artery at C1 extending intradurally. They could not remove the plaque but applied a patch graft to enlarge the artery lumen and then treated the patient with antiplatelet agents.[
Vertebral carotid transposition: A new series 2015
In 2015 Rangel-Castilla et al. reported a series of 22 patients who were refractory to medical management and who were treated for proximal vertebral artery stenosis with a vertebral carotid transposition procedure from 2005–2013. They reported a 4.5% complication rate and 4.5% restenosis rate in 9-month follow up. They state, “Despite the optimization of medical therapies and lifestyle modifications, a select subset of patients with posterior vascular circulation insufficiency remains,” echoing the theme of this review. They point out the failure of endovascular treatment in this location.[
EDAS for cerebral ischemia
In another promising area of study, Gonzalez has used the EDAS procedure laying the STA on the cerebral cortex to supply circulation to the brain in patients with MCA Stenosis or occlusion. So far his results have been very positive in showing that this therapy is superior to medical management.[
Etiologic causes and recommendations for the diagnosis of PCD
From the pathology studies reviewed above, the causes of VBI or PCD were atheroma and stenosis limiting flow,[
The conclusions that can be drawn from these studies are:
Detailed angiography or imaging is needed to show the lesions in the VBC,[ Artery to artery emboli are more common than cardiac emboli,[ Angiography must show entire cerebrovascular circulation in all 4-vessel systems and the collateral circulation to the VBC[ This information should provide an opportunity for different therapeutic options in the treatment of PCD.[
To complicate the picture of the cause of symptoms of PCD, Caplan hypothesized that atheromas obstructing major vessel branches occurred.[
RECOMMENDATIONS FOR FURTHER STUDY OF PCD
It must be recognized that PCD differs from ACD
First emergency room physicians and neurologists should be aware of the early non-specific symptomatology of PCD, which leads to a more rapid development of stroke than ACD. All such patients should be referred to neurologists with these symptoms so that a full neurological assessment can be done knowing that PCD can have rapid and devastating outcomes. Should the MRA and CTA screening test be inadequate or show stenosis of the VBC, IA angiography should be performed. All such patients should be added to a National Registry and followed. Patients who are not responsive to medical management should be referred to centers where vertebral artery surgery or posterior circulation revascularization can be performed. Since neurosurgeons with these skills are diminishing in numbers, which would mean that these patients should go to selected Comprehensive Stroke Centers. Centers with QMRA imaging should be among those where patients with PCD are referred. Patients with loss of one vertebral artery from trauma, dissection, or other causes should be studied as a subset with QMRA on a regular long-term basis to determine long-term risks of loss of one vertebral artery. It is important to remember that 65% of people have abnormalities in their circle of Willis. Patients with BAO should be considered for endovascular thrombectomy if the expertise is available and studies show its value. Since there is little evidence on the natural history of patients with PCD, precision personalized therapeutic decisions should be made on each patient and their course followed. Those patients, who are refractory to maximal medical therapy, should be referred for consideration of surgical treatment as a subset to PCD at high risk for stroke. It is hoped that from the Registry that subsets of patients can be followed and defined therapies established.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
ABBREVIATIONS
AC- Anterior Circulation
AICA-Anterior Inferior Cerebellar Artery
ASL- Arterial Spin Labeling
AT- Antithrombic therapy
BAO- Basilar Artery Occlusion
CVD- Cerebrovascular Disease
DSA- Digital Subtraction Angiography
EC-IC- ExtraCranial- Intracranial
ECVA- Extracranial Vertebral Artery
EDAS- Encephaloduroarteriosynangiosis
IA- Intra-arterial
ICH Intracerebral Hemorrhage
IVT- Intravenous Therapy
IVtPA- Intravenous Tissue Plasminogen Activator
mRS- Modified Rankin Score
MT- Mechanical Thrombectomy
NINDS- National Institute of Neurological Disorders and Stroke
NEMC-PCR- New England Medical Center Posterior Circulation Registry
PC- Posterior Circulation
PCA- Posterior Cerebral Artery
PCD- Posterior Circulation Disease
PICA-Posterior Inferior Cerebellar Artery
QMRA- Quantative Magnetic Resonance Angiography
RCT- Randomized Controlled Trial
SCA- Superior Cerebellar Artery
STA- Superficial Temporal Artery
TIA-Transient Ischemic Attacks
TNA- Transient Neurological Attacks
VAO-Vertebral Artery Occlusion
VBD- Vertebral Basilar Disease
Acknowledgment
The Authors gratefully acknowledge the review and contributions to this manuscript by Dr. Louis Caplan. The Principal Author, Dr James Ausman, dedicates this manuscript to the memory of Dr. A.B. Baker, Former Professor and Head of Neurology at the University of Minnesota and to Dr. Lyle French for their inspiration which lead to his involvement in the study of Cerebrovascular Disease.
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