8  Basilar Artery Occlusion in Bilateral Intracranial V4 Vertebral Artery Stenosis

Case 8


Basilar Artery Occlusion in Bilateral Intracranial V4 Vertebral Artery Stenosis


Clinical Presentation


A 56-year-old man was admitted to a district general hospital with acute left-sided hemiparesis, double vision, and mild nausea. The symptoms resolved except for an incomplete right oculomotor palsy. During the following hours he experienced fluctuating neurologic symptoms of transient left-sided hemiparesis, double vision, and reduced consciousness, each episode lasting for a few minutes. He had no known vascular risk factors.


Initial Neuroradiologic Findings


Cranial CT (CCT) showed normal findings without early signs of ischemic infarction, but CT angiography (CTA) demonstrated a distal basilar artery (BA) occlusion. Furthermore, severe calcifications in the distal intracranial vertebral artery (VA) on both sides were seen (not shown).


Suspected Diagnosis


Multiple transient ischemic attacks in the vertebrobasilar artery territory due to distal BA occlusion of unknown origin.


Conventional Angiography (Day 1)


On the basis of the above findings, digital subtraction angiography (DSA) was performed which confirmed the occlusion of the BA, beginning at the mid-basilar level. Collateralization of the posterior circulation was seen from the left internal carotid artery (ICA) via the left posterior communicating artery (PCoA). In addition, bilateral high-grade stenosis of the distal VA was confirmed (Fig. B8.1).


An artery-to-artery embolism originating from one of the VA stenoses was considered to be the cause of the BA occlusion. Six hours after symptom onset intra-arterial thrombolysis via the left VA was performed; administration of 50 mg recombinant tissue plasminogen activator (rt-PA) followed by 20 mg abciximab led to complete BA recanalization. Furthermore, balloon dilatation of the left high-grade VA stenosis was performed but no intraluminal stent was inserted (Fig. B8.2). The right VA stenosis was left untreated.


Clinical Course (1)


The procedure was uneventful and subsequent blood pressure was kept within the high-normal range. The residual neurologic symptoms resolved completely and no new ischemic events occurred. Laboratory testing revealed an elevated HbA1 consistent with the diagnosis of diabetes mellitus. One day after thrombolysis, a control CT scan was performed which disclosed a small right cerebellar infarction within the superior cerebellar artery (SCA) territory (Fig. B8.3). Secondary stroke prevention was started with aspirin, and the asymptomatic patient was discharged.


Six weeks later the patient was admitted to our department for the first time with repetitive transient episodes of vertigo, nausea, and gait disorder.


Questions to Answer by Ultrasound Techniques



  • Was there reocclusion of the BA after intra-arterial thrombolysis?
  • What was the postinterventional status of the left VA and of the known high-grade right distal VA stenosis?

Initial Neurosonologic Findings (Day 42)


Extracranial Duplex Sonography


B-mode sonography showed mild atherosclerotic vascular changes in both carotid arteries without evidence of stenosis. Both V2-VA segment diameters were within the normal range (left, 4.5 mm; right, 3.2 mm). Doppler spectrum analysis revealed an obviously increased pulsatility in the left V2-VA segment and only mild signs of increased pulsatility on the right V2-VA suggestive of distal flow obstruction (Fig. B8.4, Fig. B8.5, Fig. B8.6, Fig. B8.7).


Transcranial Duplex Sonography


Transtemporal insonation was impossible because of a bilaterally absent temporal bone window. The transforaminal insonation showed turbulent flow signals and increased flow velocities in both V4-VA segments, reaching a peak systolic flow velocity of 175 cm/s (insonation depth 61 mm) on the left side and 169 cm/s (insonation depth 67 mm) on the right. The BA had a low flow velocity (37/18 cm/s) but an otherwise normal flow pattern (Fig. B8.8, Fig. B8.9, Fig. B8.10; see also Video images B8.1).






Conclusion


Bilateral left-pronounced intracranial VA stenoses (>50%) without evident hemodynamic relevance. Restenosis of the left VA after balloon dilatation. No evidence of reocclusion or stenosis of the BA.









Neuroradiologic Findings


MRI could not be performed because the patient experienced severe claustrophobia. Cerebral CT did not show any new ischemic lesion. CTA confirmed the bilateral intracranial VA stenoses with severe calcification in this area (Fig. B8.11).


Clinical Course (2)


During the next few days the patient experienced further recurrent episodes of vertigo and nausea which were closely related to episodes of low blood pressure. Clopidogrel was added as a second antiplatelet agent and attempts were made to keep the blood pressure within the upper normal range. Interventional treatment with stent placement was discussed but refused by the patient. During 3 years of follow-up with dual antiplatelet therapy, no new ischemic event occurred and the neurosonologic findings remained unchanged.


Final Diagnosis


Successful intra-arterial thrombolysis in distal BA occlusion probably caused by artery-to-artery embolism from bilateral calcified intracranial VA stenoses >50%. Suspected additional hemodynamic transient ischemic attacks (TIAs) originating from the vertebrobasilar circulation.


Discussion


Clinical Aspects


The patient was a 56-year-old man with bilateral intracranial VA stenoses. An artery-to-artery embolism originated from one of these stenoses and subsequently led to a distal BA occlusion. Intra-arterial thrombolysis was successfully performed and only a small right-sided cerebellar infarct within the SCA territory remained. The case represents a special pathologic constellation within the vertebrobasilar territory because of the bilaterally affected V4-VA segments.


According to reports of several stroke databases, ischemic events of the posterior circulation account for ~20% of strokes. Only 1% of all strokes are due to BA occlusion (Bogousslavsky et al 1988, Gulli et al 2013, Moulin et al 1997, Vemmos et al 2000). The New England Medical Center Posterior Circulation Registry is the largest relevant database comprising prospectively collected data of 407 patients (Caplan et al 2004). Of these, 59% had a stroke, 24% TIA followed by stroke, and 16% had a TIA only. Ischemic strokes of the posterior circulation were caused by embolic events in 40% of cases when considering the single most likely mechanism. Of these, 60% were thought to be of cardioembolic origin, artery-to-artery embolic events originating from the posterior circulation accounted for 35%, and a mixed cause in the remaining 5% of cases. Large-artery occlusive lesions causing stroke (32%), vessel branch occlusion (14%), migraine (3%), and others (10%) were the next relevant causes (Caplan et al 2004). A tendency of embolism due to large-artery atherosclerotic disease was reported in a large registry including 8,057 patients. Here atherosclerosis was assumed to be the main cause in posterior circulation ischemia in 35%, followed by cardioembolism in 18%, and small-vessel disease in 13% (Labropoulos et al 2011).


Stenoses of the posterior circulation are predominantly found at the VA origin followed by the BA and the intracranial VA. Within the intracranial VA they are most frequently found, near the origin of the posterior inferior cerebellar artery (PICA). Bilateral stenoses, as in our case are a frequent finding (Bogousslavsky et al 1988, Caplan 1983, Müller-Küppers et al 1997). The New England Medical Center Posterior Circulation Registry reported clinical and radiologic findings of 42 patients (9.8%) with bilateral intracranial VA involvement. Of these, 18 had a bilateral stenosis, 8 had a bilateral occlusion, and 16 had a unilateral occlusion and a contralateral stenosis. Only 6 patients (14%) had isolated bilateral intracranial VA pathology. The others presented in addition occlusive vascular lesions in the BA (69%), the extracranial VA (43%), and also in the ICA (26%). Most of the stenoses were of atherothrombotic origin (Shin et al 1999). Distal BA occlusion is mostly caused by embolism. Atherosclerotic BA occlusions are usually located in its proximal and middle segment.


Similar to the anterior circulation, microembolic signals can be detected in the BA preferentially in severe intracranial VA stenosis (Hwang et al 2012).


Our patient revealed severe calcifications of both VA seen on conventional CT and also in the bone window. Despite the easy and frequently detectable pathology, clinical interest started late. Analyzing 175 ischemic stroke patients and 182 controls the highest prevalence of calcification was seen in the ICA artery in 80.4%, followed by the VA in 35.6%. Stroke patients revealed a higher prevalence of calcification than controls (92.6% versus 76.4%) (Chen et al 2007). Looking only for VA calcifications in 449 consecutive patients with stroke, more than half of them (54.6%) had visible calcifications. Calcifications in the VA were associated with higher age, larger calcified areas, and history of TIA and/or stroke (Pikija et al 2014).


In cases of chronic and slowly progressing occlusive processes, patients with distal VA stenoses develop different collateral pathways. Collateralization may occur from the anterior circulation via the PCoA or the posterior circulation via the cerebellar arteries through leptomeningeal pathways from the PICA to the SCA, and anterior spinal artery. However, often this is not sufficient, which may lead to impaired perfusion in the dependent brain territories. Consequently, patients present with recurrent stereotyped TIAs. Vertigo, dysarthria, ataxia, and double vision are the most frequent symptoms, which may be aggravated by orthostatic or antihypertensive therapy (Caplan 1996). Shin and coworkers (1999) found that 81% of patients in the group with TIAs had bilateral VA pathology; 38% of the TIAs were isolated events, and the remainder occurred before or after manifestation of stroke. In most TIAs a hemodynamic cause was suspected (Shin et al 1999). As in our case, transient vertigo and ataxia were the most frequently found clinical symptoms. The main components of the vestibulocerebellar system, located in the cerebellum and brainstem, derive their blood supply from the distal VA via penetrating branches and the PICA and are quickly affected by a reduced antegrade perfusion. However, the diagnosis of a hemodynamic impairment caused by steno-occlusive processes within the vertebrobasilar circulation requires careful clinical assessment as well as good imaging analysis. In fact, it seems to be less frequently present than previously assumed. In the New England Posterior Circulation Register a hemodynamic ischemia, predominantly caused by bilateral intracranial VA stenosis, was reported in 13 of 407 patients (Savitz and Caplan 2005).


If a completed stroke occurs, the infarct pattern depends on the site of the vascular pathology. Medullary infarctions or infarcts of the PICA territory are observed if the stenotic process is located proximal to, or directly at the origin of the PICA. Ischemia within the BA, SCA, and posterior cerebral artery (PCA) territory occur more often in stenotic processes distal to the PICA branch. Artery-to-artery embolic events from atheromatous plaques located in the intracranial VA may also result in distal patterns of infarction. In our patient, a VA-derived embolus caused a distal BA occlusion with clinically fluctuating signs of a “top-of-the-basilar-syndrome” (Caplan 1980, Mehler 1989). In cases of persisting occlusion this may lead to ischemic infarctions in the upper pons, mid-brain, cerebellar SCA territory, thalamus, and the cortical PCA territory. However, the extent may vary, as can be seen in our patient who only suffered a partial SCA infarction. From this we can assume that although the occlusion began at the mid-basilar level, it must have extended to the head of the BA. We can also conclude that our patient’s clinical symptoms were indicative of distal BA involvement, as they consisted mainly of a mesencephalic dysfunction (transient third nerve palsy and fluctuation in consciousness). Because of the fluctuating symptoms, lack of ischemic signs on cerebral CT, and verification of the BA occlusion by DSA, an intracranial thrombolysis was performed which led to complete recanalization 6 hours after the onset of his symptoms. Furthermore, balloon dilatation of the left high-grade VA stenosis was performed.


The treatment recommendation in thromboembolic occlusions of the BA is similar to those in the anterior circulation and includes intravenous thrombolysis with recombinant tissue plasminogen activator (IV rt-PA), intra-arterial thrombolysis, and endovascular thrombectomy.


For treatment decision, the clinical severity (assessed by the NIHSS score) plays an important role. However, the NIHSS score has some limitations if applied to ischemic stroke of the posterior circulation. Strokes within the anterior circulation usually attain higher scores because of cortical signs and/or motor deficits. Posterior circulation ischemia often scores lower as cranial nerve deficits and ataxia without paresis are weighted lower. Despite relatively lower NIHSS scores, patients with posterior circulation stroke often show a worse outcome (De Marchis et al 2011, Sato et al 2008).


The recently published Third International Stroke Trial (IST 3) reported on thrombolysis using IV rt-PA within a 6-hour time window. It showed an improvement in the functional outcome but no reduction in mortality. A limiting factor, however, might have been that only 246 of the 3,025 patients included suffered from stroke in the posterior circulation (Sandercock et al 2013).


Untreated BA occlusion is a neurologic emergency, mostly with a fatal outcome. This is why available treatment strategies have also been applied beyond the therapeutic time windows consented for the anterior circulation. Lindsberg and colleagues applied systemic rt-PA thrombolysis in patients with vertebrobasilar occlusion up to 12 hours after disease onset in sudden disturbance of consciousness and tetraparesis and up to 48 hours after disease onset in those with gradually increasing brainstem symptoms (Lindsberg et al 2004). In this series including 43 patients with a BA occlusion, 52% showed a BA recanalization. The mortality after 3 months was 40%, and 22% of patients achieved a good clinical outcome, being independent in all functions of daily living. In patients with a stuttering course and no early infarct signs, the time window for intra-arterial and systemic thrombolysis may even be extended at least to up to 48 hours after onset of symptoms (Lindsberg and Mattle 2006). In a large prospective study evaluating 184 consecutive patients with angiography-proven BA occlusion and subsequent IV rt-PA treatment followed by concomitant full-dose heparin administered within up to 48 hours achieved good clinical outcomes in 50% of cases, independent of the time onset of treatment. Factors associated with a poor outcome were higher age and bad clinical status, a lack of recanalization, a history of atrial fibrillation, and a symptomatic ICH (Strbian et al 2013). Currently, official guidelines in the United States and Europe recommend intravenous thrombolysis within 4.5 hours of symptom onset, based on the results of the ECASS III study.


Improved recanalization rates and clinical outcomes were also reported for intra-arterial thrombolysis when compared with medical therapy with an antiplatelet agent. A meta-analysis compared the results of intravenous and intra-arterial thrombolysis within the posterior circulation. It demonstrated that recanalization rates were significantly better if intra-arterial thrombolysis was used instead of intravenous thrombolysis (65% versus 53%). However, survival rates did not differ significantly between the two groups (45% versus 50%) and both groups had a similar proportion of good clinical outcome (24% versus 22%) (Lindsberg and Mattle 2006). Independent of the applied treatment strategy, the proportion of patients with a good clinical outcome was higher if recanalization had occurred (38% versus 2%). The Basilar Artery International Cooperation Study (BASICS) also found no evidence of superiority for intra-arterial thrombolysis over intravenous thrombolysis (Schonewille et al 2009).


In addition to the above-mentioned treatment regimens, a combination of therapies described as “bridging” therapy has been proposed for the posterior circulation. Bridging combines intra-arterial rt-PA, intravenous abciximab, and, if applicable, a balloon dilatation or stent placement. Compared with IV rt-PA alone, a study of 47 patients demonstrated similar recanalization rates (72% versus 68%), a better clinical outcome (34% versus 17%), and a significant lower mortality (38% versus 68%) for the combined treatment group (Eckert et al 2005).


As described above, a successful recanalization is closely related to the clinical outcome of the patient. A meta-analysis of 53 studies with reported recanalization rates calculated that a successful recanalization increases the chance of a good clinical outcome four- to fivefold while decreasing mortality accordingly (Rha and Saver 2007). Also, the previous thrombectomy studies demonstrated that patients with early recanalization perform better than those with delayed recanalization.


For these reasons, clinical research in recent years has predominantly focused on mechanical recanalization strategies, which can achieve high recanalization rates for all reported vessel segments.


First experiences with a new device for aspiration thrombectomy (the Penumbra system) were reported in 12 patients with acute BA occlusion who had previously received IV rt-PA thrombolysis. Thrombectomy was achieved in almost all cases while vessels remained occluded in 64% of the conservatively treated patients (Roth et al 2011). Meanwhile, the more modern stent retrievers (Trevo, Solitaire) have yielded superior results compared with the coil-retriever (Merci) and the aspiration catheter (Penumbra). However, data concerning mechanical recanalization of the posterior circulation are scarce. Studies with negative results include either no patients with a vessel occlusions of the posterior circulation any (MR Rescue study) or only very few (IMS III: 2%, SYNTHESIS expansion: 8%). Criticism also arose concerning study design as well as patient and device selection. The first and more recent studies with positive results for mechanical recanalization (ESCAPE, EXTEND IA, SWIFT-PRIME, MR CLEAN) exclusively recruited patients with ischemic stroke of the anterior circulation. Studies analyzing mechanical recanalization of the posterior circulation are on their way and their results are eagerly anticipated (for further information on mechanical thrombectomy, see Case 10 and Chapter 6, “Technical Aspects of Mechanical Thrombectomy” under “Digital Subtraction Angiography”).


Medical secondary stroke prevention and treatment of vascular risk factors in general do not differ from the concepts of the anterior circulation. Patients with a symptomatic stenosis in the vertebrobasilar vascular system (i.e., with a VA or BA stenosis >50%) have a threefold risk of recurrent stroke for within 90 days after stroke if compared with those without a detectable stenosis. Especially intracranial stenoses show an early relapse rate of up to 33% while early relapses in extracranial stenoses occur in only 16.2% (Gulli et al 2013).


In our patient, repetitive symptoms occurred during aspirin treatment. They were considered primarily hemodynamic on the basis of bilateral >50% V4-VA stenoses and a fluctuating blood pressure. Nonetheless, in view of the intracranial stenosis location dual antiplatelet therapy was initiated, adding clopidogrel which was continued for several years.


The latter decision followed the results of the CHARISMA study (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization Management and Avoidance) which included a total of 9,478 patients after myocardial infarction, ischemic stroke, or symptomatic peripheral arterial disease. The trial revealed a considerably lower rate of cardiovascular death, myocardial infarction, or stroke in the clopidogrel plus aspirin arm compared with the placebo plus aspirin arm (7.3% versus 8.8%) during a median follow-up of 27.6 months, while there was no significant difference in the rate of severe bleeding (1.7% versus 1.5%; Bhatt et al 2007). Similar results were seen in the recently published CHANCE study (Clopidogrel in High-Risk Patients with Acute Non-disabling Cerebrovascular Events) which included 5,174 patients with minor stroke or TIA. A combination of clopidogrel and aspirin compared with aspirin alone showed a moderate superiority for the former in preventing of relapse incidents of all vascular territories (8.2% versus 11.7%) (Y. Wang et al 2013). The results of the SAMMPRIS study (Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis) add further arguments in favor of a temporary dual platelet inhibition therapy after minor stroke or TIA in patients with an intracranial stenosis (Chimowitz et al 2011) (for further reading, see also Case 5).


In our patient, balloon dilatation was performed in the left intracranial VA but a restenosis of the dilated vessel occurred. Restenosis has been reported in approximately one-third of cases after intracranial stenting (Jiang et al 2007, SSYLVIA Study Investigators 2004). Stenting seems not to be superior to balloon dilatation with respect to restenosis rates, but stroke rates at follow-up might be lower after stenting procedures. Furthermore, the periprocedural stroke risk is higher for intracranial VA stenosis and BA stenosis than for proximal VA stenosis (Eberhardt et al 2006). The SAMMPRIS study mentioned above showed a clear inferiority for the stent treatment of a symptomatic intracranial stenosis compared with aggressive medical therapy: 60 out of 451 patients included (13%) had a stenosis of the intracranial VA or the BA. Subgroup analysis reported a particularly high periprocedural stroke risk of 20.8% in BA stenosis compared with 6.7% in all other vessels. In the majority of cases, an occlusion of paramedian perforators was observed (Derdeyn et al 2013, Fiorella et al 2012). According to the current data, routine stenting or balloon dilatation of vessels in symptomatic stenoses of the posterior circulation cannot be recommended. According to the SAMMPRIS study, aggressive medical treatment with temporary dual platelet inhibition is the treatment of first choice. Whether a secondary prophylactic interventional therapy in the vertebrobasilar artery might be another reasonable approach is currently being studied in the VIST trial (Vertebral artery Ischaemia Stenting Trial) and the VAST trial (Vertebral Artery Stenting Trial) (for further information on intracranial stenting, see also Case 5).


Angiologic and Anatomic Aspects


In our case, the transcranial color-coded sonography (TCCS) assessment of both intracranial V4-VA stenoses was uncomplicated. The cut-off for a 100% confident detection of a >50% stenosis is >120 cm/s (Baumgartner et al 1999). Both VAs in our patient revealed systolic flow velocities of around 170–180 cm/s, clearly above these cut-off values. There are no published data for a more detailed grading. In ultrasound examination, a flow profile analysis of pre- and poststenotic vessel segments can give valuable additional information. The extracranial VA profiles in our patient revealed an increased pulsatility, pronounced on the left side, as well as a small left-sided retrograde flow component. The BA itself did not show an obvious poststenotic flow pattern. Taking this information into account, a hemodynamic relevant stenosis of at least 70% in the left V4-VA segment and a stenosis of 50–70% in the right V4-VA segment had to be assumed. In hemodynamic relevant stenoses of both VAs a clear poststenotic BA flow pattern would have been expected. Ultrasound assessment of the intracranial VA segment may be limited in patients who are uncooperative or have impaired neck mobility, or those with a large neck circumference. Furthermore, V4-VA segment elongations, frequently found in elderly people, might hinder unequivocal vessel identification and lead to confusion between VA and, for example, a prominent PICA. The quality of vessel insonation in our patient was poor. As the transforaminal insonation approach is not primarily limited by a bone window, insonation in our patient was most probably impaired by the known calcified plaques, hindering long-segmented vessel visualization. Despite these limitations, flow signals in the stenosis were detectable, probably facilitated by the routine use of low insonation frequencies during transforaminal insonation and possibly inhomogeneities within the calcifications. If VA evaluation is difficult in the acute posterior stroke setting, delays should be avoided and further diagnostic steps (e.g., CTA or MRA) should be initiated; however, analysis of the intracranial VA and the transitional segment between the V3 and V4 segments may also be difficult with the latter two techniques. As seen in our patient, a distinct and long circumferential calcification can hinder CTA to assess a V4-VA stenosis. In these cases, dual-energy CT might be advantageous, as reported for calcified carotid stenoses (Uotani et al 2009). Also, the analysis of the axial source images or a combined approach with MRA may be of help (Hirai et al 2002). Compared with the gold standard DSA, time- of-flight (TOF) MRA applied for the detection of intracranial VA stenoses demonstrates a lower diagnostic sensitivity and specificity (84% and 93% versus 74% and 82%) than for the detection of extracranial VA stenoses (92% and 96% versus 100% and 90%). Increasingly TOF-MRA is being replaced by contrast-enhanced MRA techniques. The latter show a better image contrast, require less time, and are therefore less susceptible to movement artifacts (Ersoy et al 2003). Compared with carotid artery analysis, contrast-enhanced MRA of the vertebrobasilar circulation is, however, less sensitive and specific in detecting steno-occlusive processes (Yang et al 2005). In equivocal or conflicting diagnostic constellations, catheter angiography may be required (for further information on assessment of intracranial stenoses, see also Case 5).


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Jun 20, 2018 | Posted by in NEUROSURGERY | Comments Off on 8  Basilar Artery Occlusion in Bilateral Intracranial V4 Vertebral Artery Stenosis

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