Current Treatment Options in Cardiovascular Medicine

, Volume 13, Issue 3, pp 261–267

Dolichoectasia of the Intracranial Arteries

Authors

  • Hyung-Min Kwon
    • Department of Neurology & Stroke Center, Boramae Medical Center, College of MedicineSeoul National University
    • Department of Neurology & Stroke Center, Boramae Medical Center, College of MedicineSeoul National University
Cerebrovascular Disease and Stroke

DOI: 10.1007/s11936-011-0123-z

Cite this article as:
Kwon, H. & Lee, Y. Curr Treat Options Cardio Med (2011) 13: 261. doi:10.1007/s11936-011-0123-z

Opinion statement

Dolichoectasia is a dilatation and elongation of the arteries, usually affecting intracranial basilar and vertebral arteries. It may cause posterior circulation stroke or transient ischemic attacks independent of atherosclerotic disease. Compression of cranial nerves or brainstem leads to hemifacial spasm, trigeminal neuralgia, or brainstem dysfunction (temporary or permanent). Intracranial bleeding is another possible manifestation. In general, the mortality and morbidity is higher in patients with dolichoectasia. Progression of arterial dilatation or elongation is an ominous sign for poor prognosis. Optimal treatment for vertebrobasilar dolichoectasia is uncertain. Adequate control of blood pressure may prevent ischemic or hemorrhagic stroke. In case of ischemic stroke, antiplatelet treatment is indicated for the prevention of recurrent stroke. However, the risk of hemorrhagic stroke should be considered in patients with severe forms of dolichoectasia. Close observation and follow-up neuroimaging is recommended to monitor the progression of the disease and appearance of new ischemic or hemorrhagic lesions. Surgical decompression may be reserved for the medically intractable patients with trigeminal neuralgia or hemifacial spasm.

Introduction

Dolichoectasia (“dolicho” meaning elongated, and “ectatic” meaning dilated) is an uncommon vasculopathy mainly involving intracranial arteries. By definition, increases in the diameter and length of the large arteries are essential components. Recently, it has also been referred to as “dilatative” arteriopathy because widening is a more important feature than elongation or tortuosity [1]. The prevalence of intracranial dolichoectasia is approximately from 0.06% to 5.8% in the general population [2, 3]. However, it is more frequently found (10%–12%) in patients with stroke [4, 5]. Angiographic and post-mortem studies revealed that the vertebral artery (VA) and basilar artery (BA) are particularly affected, although the middle cerebral artery (MCA) or internal carotid artery (ICA) may also be involved [6, 7]. Dolichoectasia is more common in the elderly, and atherosclerotic change is not infrequently associated. However, it has also been described in patients without atherosclerotic changes or even in children [8, 9], suggesting a multi-factorial etiology.

Vertebrobasilar dolichoectasia (VBD) may be asymptomatic, or it may be associated with clinical manifestations such as posterior circulation stroke or transient ischemic attacks (TIA), intracranial bleeding, cranial nerve disorders (hemifacial spasm or trigeminal neuralgia), compression of brainstem, or obstructive hydrocephalus.

Diagnostic criteria

  • There are no unified criteria for the diagnosis of dolichoectasia. However, widely accepted criteria were proposed first with the advent of CT technique [10]. VBD can be defined as having three components: 1) arterial diameter, 2) height (vertical level of the basilar bifurcation), and 3) lateral displacement of the BA. Diameter of BA ranges from 3.2 to 4.5 mm in autopsy series [11, 12]. However, it is different whether measured by angiography (2.7 mm) [2] or by contrast-enhanced CT scans (3.2 mm) [10]. Smoker et al. [10] suggested 1.9 to 4.5 mm as normal range by CT measurement [10]. Actually, axial CT scans may show an ectatic BA as it courses transverse, so this may represent larger than real diameter if considering the combined effects of partial-volume averaging. Therefore, diameter >4.5 mm in any location along its course can be regarded as ectatic. Vertical elongation and lateral displacement may be graded by the position of the basilar bifurcation and lateral margin of BA (Table 1, Fig. 1) [10, 13]. This scoring system is easy to apply and helpful to estimate the severity to compare the serial changes. Except for BA, there are no validated criteria for other vessels. Passero and Rossi [14] have suggested following criteria: ICA >7 mm, MCA >4 mm, and VA >4 mm.
    Table 1

    Scoring system to grade lateral displacement and vertical elongation of basilar artery

    Score

    Lateral displacement (most lateral position of BA)

     

    Vertical elongation (plane of BA bifurcation)

    0

    Midline throughout

    0

    At or below dorsum sellae

    1

    Medial to lateral margin of clivus or dorsum sellae

    1

    Within suprasellar cistern

    2

    Lateral to lateral margin of clivus or dorsum sellae

    2

    At the level of third ventricle floor

    3

    Within cerebellopontine angle cistern

    3

    Indenting and elevating floor of third ventricle

    BA basilar artery

    (Data from and Smoker et al. [10] and Giang et al. [13].)

    https://static-content.springer.com/image/art%3A10.1007%2Fs11936-011-0123-z/MediaObjects/11936_2011_123_Fig1_HTML.gif
    Figure 1

    Grade of basilar artery dolichoectasia based on magnetic resonance source images. Lateral displacement of the basilar artery (panel A) and height of basilar bifurcation (panel B).

Pathology and pathogenesis

  • Dolichoectatic arteries have an abnormally large external diameter with a thin arterial wall, and they sometimes bear an intraluminal thrombus or an atherosclerotic plaque [8]. On microscopic examination, the main findings are in the media, with rarefaction of the elastic tissue and degeneration of the internal elastic lamina [15, 16]. According to the autopsy study, patients with dolichoectasia tend to have a disorder of the arterial tree, including ulcerated plaques of the aortic arch, basilar plaques, and small vessel disease [17]. Sclerosis and hyalinosis in the deep small arteries (<300 μm) was nearly four times more frequent in patients with dolichoectasia, which supported a previous study evaluated by MRI [5]. The strong, independent association between dolichoectasia and small vessel disease may be partly explained by the fact that both conditions affect the media of the arteries.

  • Patients with dolichoectasia tend to have larger diameters of thoracic aortas than patients without dolichoectasia [18]. In addition, abdominal aortic aneurysm is frequently found (1 in 3) [8], and concurrent ectasia of coronary arteries also has been reported [19]. These findings suggest that dolichoectasia, as a dilatative arteriopathy, may not be limited to intracranial arteries but may be a systemic manifestation of vascular ectatic disease.

  • Matrix metalloproteinases (MMPs) has been suggested as a possible candidate for pathogenesis of these conditions of arterial dilatation. In an autopsy study, cells that contained MMP-3 (macrophages and microglia) were more often present around hyalinosclerotic, small perforating arteries and areas of severe white matter damage corresponding to leukoaraiosis [20]. Recent study has demonstrated that dolichoectasia is associated with low MMP-3 plasma levels and with the 5A/6A polymorphism of the promoter region of MMP-3 [21•]. These results suggest that MMP-3 may play a role in intracranial arterial dolichoectasia.

  • The relation between dolichoectasia and atherosclerosis is a matter of debate, atherosclerosis being either the cause or the consequence of dolichoectatic processes. Atherosclerosis primarily involves the intima of large- and medium-size arteries, whereas dolichoectasia involves mainly the media of intracranial arteries. Both have several vascular risk factors in common, such as old age, male sex, and hypertension, which may explain their co-existence. However, carotid atherosclerosis assessed by ultrasound examination was not associated with dolichoectasia in patients with stroke [5]. The autopsy study also confirmed the lack of association between intracranial dolichoectasia and cerebral large-artery atherosclerosis, except for basilar plaques [17].

Clinical manifestations

Ischemia and infarction

  • Stroke or TIA in posterior circulation is the most common clinical manifestation in patients with VBD. The most frequent location of the infarct is pons (2 of 3 instances). Cerebellum, midbrain, thalamus, or superficial posterior cerebral artery territory also can be involved [2224]. Previously, two mechanisms on the basis of the imaging and angiographic findings were suggested: 1) infarcts in distal territories (thalamus, superficial PCA territory, cerebellum) that may be associated with artery-to-artery embolism [25, 26], and 2) brainstem and cerebellar infarcts that may be associated with atherothrombotic occlusion at the origin of BA branches (branch atheromatous disease) [27]. However, according to the recent study, ectasia of BA (>4.5 mm) was more frequent in patients with paramedian infarct affecting anterior surface of the pons compared with deep lacunar infarct in patients with VBD without underlying stenosis of BA or VA [28•]. These results indicate that ectasia of BA may be a significant cause of paramedian pontine infarct irrespective of atherosclerotic narrowing. Several pathophysiologic mechanisms of infarct can be postulated. In the dilated, elongated, and tortuous segment of the arteries, blood flow may be stagnant. According to the transcranial Doppler studies, mean flow velocity of BA is decreased in patients with VBD [29], and this is correlated with distal lesions involving thalamus, midbrain, and posterior cerebral artery territory [24]. Reduced blood flow may precipitate thrombus formation within dilated segments leading to obstruction of penetrating branches or to embolization into distal branches or perforators. Hemodynamic impairment may also occur and can lead to transient ischemic symptoms like recurrent vertigo [30]. On the other hand, elongation and angulation of the arteries can mechanically stretch and distort the orifices of the penetrating branches, which may reduce blood flow leading to lacunar infarct. The strong association between intracranial dolichoectasia and small vessel disease needs to be focused. According to the Génétique de l’Infarctus Cérébral (GENIC) study, in which 510 patients with stroke were recruited, lacunar infarct was more frequent in patients with intracranial dolichoectasia compared with patients without dolichoectasia (adjusted odds ratio of 2.89; 95% CI, 1.29–6.46) [5]. Dolichoectasia is independently associated with cerebral small vessel disease, including lacunar infarcts, multiple lacunes, severe leukoaraiosis, and severe état crible (dilated Virchow-Robin spaces around penetrating arteries) [5, 31].

Intracranial bleeding

  • Intracerebral hemorrhage (ICH) or subarachnoid (SAH) hemorrhage is an uncommon manifestation of intracranial dolichoectasia. Pathologic changes in the arterial wall, consisting primarily in defects in the internal elastic lamina with thinning of the media secondary to smooth muscle atrophy [15], may predispose patients to intracranial bleeding. Actually, the autopsy finding of one fatal case proved rupture of dolichoectasia as the cause of bleeding [32]. According to the prospective cohort study (156 patients, mean follow-up 9 years), 32 hemorrhagic strokes (26 ICH and 6 SAH) were reported in 28 patients, including 4 patients with recurrent hemorrhage [32]. Thalamus was the most prevalent site (42%), followed by occipital/temporal lobes (19%), or brainstem/cerebellum (19%). All SAHs were confined to one or more cisterns around the brainstem, suggesting a pattern of peri-mesencephalic SAH. Underlying saccular aneurysms were usually absent on diagnostic angiography. One patient with SAH and four patients with ICH died of the first hemorrhagic event, whereas two patients died of a recurrent hemorrhage. Multivariate analysis found an association between intracranial bleeding and maximum diameter or degree of lateral displacement of the BA, hypertension, use of antiplatelet or anticoagulant agents, and female sex [32]. These results may suggest that adequate blood pressure control may be helpful to prevent hemorrhagic stroke. And caution is warranted to prescribe antithrombotic agents in patients with severe forms of VBD.

Cranial nerve disorders

  • Hemifacial spasm is the relatively frequent associated condition that is related to vascular compression of the root entry zone of the facial nerve at the brain stem by elongated tortuous vessels [33]. In one study involving 648 patients undergoing microvascular decompression for hemifacial spasm, 24% was ascribed due to compression by VA, although the presence of dolichoectasia was uncertain [34]. However, another recent series observing 1642 patients demonstrated that direct compression by VBD was found only in 0.7% [35]. Although decompressive surgery is effective in this situation, manipulation of ectatic arteries and traction of small perforators may result in permanent facial weakness, deafness, or stroke. Furthermore, due to its poor mobility of the artery, recurrence may occur in case of insufficient decompression [33, 35].

  • Compression of trigeminal nerve root by dolichoectatic VA (or rarely BA) is a known cause of trigeminal neuralgia. Pathologic examination revealed a zone of chronic demyelination and some remyelination in the proximal part of the root, near its junction with peripheral nerve [36]. Microvascular decompression may relieve symptoms, but the partly aberrant nature within the region of compression may result in the persistence of symptoms in some patients despite of the surgical treatment [36].

  • Oculomotor dysfunction may occur due to compression of oculomotor or abducens nerve. Although isolated abducens nerve palsy has been reported [37], oculomotor paresis in this situation is usually associated with other neurologic deficits.

Compression of brain stem

  • Dilated VAs can directly compress the medulla oblongata, causing transient or persistent symptoms. Motor weakness, vertigo, or gait ataxia is the usual manifestation [38]. Tingling sense, tinnitus, hoarseness, or headache may occur infrequently. The clinical findings are not well correlated with the severity or extent of impingement. Compression may be gradual, allowing for adaptation, which may reduce the risk of damaging respiratory and autonomic centers in the medulla. Surgical decompression has often been unsuccessful and fraught with complications, although it may provide temporary symptom relief. Progression of deficits or recurrence of symptom was rare among the medically treated patients [38].

Natural course and prognosis

  • The long-term prognosis of patients with VBD is not well known. In a small retrospective cohort (45 patients, median follow-up 5 years), the risk of stroke or TIA (odds ratio of 20.6) and mortality (odds ratio of 3.6) was higher in patients with VBD compared with controls [39]. According to the well-designed prospective study (156 patients, mean follow-up 12 years), 60% experienced at least one event: 75 patients had stroke (59 ischemic and 21 hemorrhagic), 31 patients had new compressive symptoms, and 2 patients had hydrocephalus [14]. The cumulative 10-year risk of a first recurrent stroke was 56%. Events were significantly associated with the severity of dolichoectasia of the BA. Progression of dolichoectasia was observed in 43%, which was associated with a higher morbidity and mortality [14]. Progression was more likely to be observed in younger, symptomatic patients, or already advanced cases at the time of diagnosis. Another study also suggested that symptomatic compression at the initial diagnosis, transitional or fusiform shape, or initial diameter is associated with progression [40]. In summary, the long-term prognosis of patients with VBD depends on the severity of dolichoectasia at diagnosis and its evolutionary nature, which confers a higher risk of death or stroke.

Therapeutic considerations

  • Currently, there is no specific treatment to prevent progression of VBD. Although specific risk factors for VBD are not well documented, adequate control of blood pressure may be helpful to prevent ischemic or hemorrhagic stroke in patients with VBD. There is no current evidence that antiplatelet therapy may be effective for primary prevention of ischemic stroke in patients with VBD. However, antiplatelet therapy may be considered for the prevention of recurrent stroke in patients with current or previous stroke. As in the current treatment guideline, aspirin or other antiplatelet regimens can be recommended as the first-line therapy for prevention of recurrent stroke [41]. Unlike atherothrombotic stroke, however, potential risk of bleeding may be considered in patients with severe forms of VBD. In particular, long-term use of combined antiplatelet agents or anticoagulants may not be recommended. Patients with previous hemorrhagic stroke or with progressing dolichoectasia also must proceed with caution. Optimal antiplatelet treatment in these patients remains to be determined by further studies.

  • Symptoms caused by compression of cranial nerves (trigeminal neuralgia or hemifacial spasm) may be alleviated by decompressive surgery. However, due to its potential complications, surgical treatment should be reserved for intractable cases despite of adequate medical therapy. Surgical decompression may not be considered for brainstem compression without critical symptoms. Close observation and follow-up neuroimaging is recommended to monitor the progression of dolichoectasia and the appearance of new ischemic or hemorrhagic lesions. Treatment of patients with VBD needs to be individualized by patient characteristics, symptoms, risk of treatment and compliance.

Disclosure

The authors report no potential conflicts of interest relevant to this article.

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© Springer Science+Business Media, LLC 2011