Posterior Circulation Infarcts in Patients With Vertebrobasilar Dolichoectasia

Subjects and Methods

We studied 40 consecutive stroke patients with associated VBD. All were evaluated by CT scan (n=9), MRI (n=6), or both (n=25). Eighteen patients underwent additional angiographic examination performed by the Seldinger method, and 11 underwent MRA. Other investigations included standard blood tests, Doppler ultrasonography, ECG, and transthoracic echocardiography. MR was performed with a 0.5-T superconducting magnet unit with use of spin-echo, multi-echo, and FAST techniques. The images (T1- and T2-weighted and proton density) were obtained in the sagittal, axial, and coronal planes. Slice thickness was 5.0 mm, with a 2.0-mm interval between successive slices. According to Smoker et al,²² the BA was judged elongated if at any point along its course it lay lateral to the margin of the clivus or dorsum sellae or bifurcated above the plane of the suprasellar cistern. Ectasia was diagnosed if the diameter of the artery was greater than 4.5 mm.

The following risk factors for cerebrovascular disease were examined: history of hypertension (previous diagnosis of arterial hypertension, ie, systolic blood pressure >160 mm Hg or diastolic >90 mm Hg or both and/or past or present use of antihypertensive agents), diabetes mellitus (previous diagnosis of diabetes and/or past or present use of antidiabetic agents), current smoking, alcohol abuse (ingestion of >400 mL/wk pure ethanol), hyperlipidemia (cholesterol level of >250 mg/100 mL or triglyceride level of >180 mg/100 mL or both), previous coronary artery disease (or myocardial infarction), and potential cardiac source of embolism.

Ischemic lesions in the posterior circulation were classified according to the anatomic site and the presumed vascular territory involved using the templates proposed by Pullicino,²³ Tatu et al,²⁴ and Damasio.²⁵ The diameter of the BA, height of bifurcation, and lateral displacement were evaluated as suggested by Smoker et al.²² The height of the BA bifurcation was scored as 1 (within the suprasellar cistern), 2 (at level of third ventricle floor), or 3 (indenting and elevating the floor of the third ventricle); lateral displacement was scored as 1 (medial to lateral margin of clivus or dorsum sellae), 2 (lateral to lateral margin of clivus or dorsum sellae), or 3 (in cerebellopontine angle cistern). A global index of dolichoectasia was calculated by adding the single scores.

Some clinical and imaging findings (parameters of the BA, presence of hypertension, and presence of atherosclerotic changes of the posterior circulation) were compared with those found in a group of 40 patients (9 women and 31 men; mean age, 61.6±8.6 years; median age, 63.0 years; range, 45 to 82 years) with VBD but no history of cerebrovascular events. None of these patients showed evidence of ischemic lesions in the posterior circulation on CT (n=9) or MRI (n=31) examinations. Sixteen patients also underwent conventional angiographic examination.

The χ² test was used in the statistical procedures.

Results

The 40 patients (9 women and 31 men) ranged in age from 47 to 83 years (mean, 62.8±8.9 years; median, 63.0 years). Of these patients, 25 had experienced no previous cerebrovascular events. Twelve patients had suffered one or more previous transient ischemic attacks, and 3 patients had previous cerebral hemorrhages (1 thalamic, 1 putaminal, and 1 lobar). At the time of stroke all patients without previous history of cerebrovascular events and the 3 patients with previous cerebral hemorrhage were not being treated with antithrombotic drugs. Among the 12 patients with previous transient ischemic attacks, 5 were treated with aspirin (325 to 500 mg/d) and 5 with dipyridamole, while 2 patients were not under treatment at the time of stroke.

Discussion

The relationship between cerebrovascular events and VBD has been described in occasional cases and in a few patient series. In those reports with sufficient clinical and imaging data,^{3 4 5 8 9 10 11 13 15 26 27 28 29 30 31 32} the most frequently described ischemic lesion was brain stem infarction, observed in 39 of 56 patients. Ten patients were reported to have cerebellar infarcts, 4 thalamic infarcts, and 3 infarcts in the superficial PCA territory (Table 5⇓). Brain stem infarcts were most often located in the pons (29 of 39). Other authors have observed VBD in study series of patients with cerebellar,^{33 34} pontine,³⁵ medullary,^{36 37} and thalamic³⁸ infarcts or in patients with posterior circulation strokes.³⁹

Unlike those in other series,^{4 9 11 13} our patients showed a higher incidence of supratentorial infarcts, especially in the superficial PCA territory. This discrepancy may result from many factors, including different patient enrollment criteria and different imaging methods. MRI has certainly aided recognition of small infarcts not detectable by CT. Moreover, in patients with acute stroke, CT scan often cannot detect the simultaneous presence of VBD unless the BA has calcifications or a contrast medium is used.

The precise pathophysiology of cerebral ischemic events associated with VBD is not clear. In this condition, mechanisms commonly observed in patients with cerebrovascular disease, such as arteriolar lipohyalinosis, obstruction by atheroma or intraluminal thrombus, and artery-to-artery embolism, may be operant. However, in VBD other specific mechanisms, such as distortion of branches of the BA due to elongation and tortuosity of this vessel and hemodynamic factors related to the significant reduction of flow velocity in the BA, may contribute to ischemia.

On the basis of the imaging and angiographic findings and exclusion of patients with other potential cause of stroke, two pathophysiological mechanisms of infarction can be identified in our series: (1) infarcts in distal territories (thalamus, superficial PCA territory, cerebellum) that may be associated with artery-to-artery embolism^{8 28} and (2) brain stem and some cerebellar infarcts that may be associated with atherothrombotic occlusion at the origin of BA branches (branch atheromatous disease).⁴⁰

Our study reveals three interesting aspects. The first is the fact that the infarcts located in the PCA territory were significantly associated with more severe ectasia and vertical elongation of the BA than those located in territories supplied by branches of the basilar or vertebral arteries. This suggests the involvement of hemodynamic or thromboembolic mechanisms related to the reduced blood flow velocity in severe dolichoectasia (as demonstrated by angiographic study and transcranial Doppler examination)¹² and to the distortion of the PCAs and their small branches. Another aspect suggesting a hemodynamic mechanism is the fact that half of the patients with infarcts in the superficial PCA territory had occlusion or severe stenosis of the anterior circulation. This feature was also observed by Steel et al⁸ in a patient with an occipital infarct associated with VBD and a severe stenosis of the internal carotid artery.

Among infratentorial infarcts, we observed that the majority of the lesions in the arterial territories supplied by branches of the BA were contralateral to the side of the lateral displacement of the BA, which suggests a relationship between ischemia and distortion and/or stretching of the branches of the BA.

Some authors^{21 41} have suggested that atherosclerotic degeneration of the vascular wall, either alone or associated with arterial hypertension, is the initial pathogenetic factor in the development of this condition. Other authors maintain that atherosclerosis does not play a substantial role in the pathogenesis of arterial ectasia and that VBD is a congenital anomaly. The second hypothesis is backed by histological studies that show defects in the internal elastic lamina, with thinning of the media secondary to smooth muscle atrophy^{20 32 42} ; by the frequent absence of atherosclerosis^{42 43} ; and by the occurrence of arterial ectasia in all age groups.^{13 44 45 46 47} Furthermore, VBD may be (1) a component of generalized ectasia of the cerebral vessels, as indicated in our and other series^{1 4 6 7 10 11 26 32 42 43 46 48} ; (2) associated with aneurysm of the abdominal aorta^{4 13 21 32 43 44 46} ; or (3) associated with ectasia of other vascular districts,^{43 46} which suggests a more diffuse arterial defect.

It seems likely that a defect in the development of the arterial wall is responsible for ectasia, which may also be favored by arterial hypertension, associated in some cases with an atheromatous process that further damages the elastic elements. Thus VBD may occur in the absence of atheroma or with superimposed atheromatous changes, as in the present series and others.^{1 21 42 43 44} Superimposed atheromatous changes may have an important role in precipitating ischemia, as suggested by our comparison of VBD patients with and without stroke, which showed that ischemic complications of VBD were significantly more often observed in patients who had superimposed atheromatous changes of the posterior circulation. However, the present study shows that other factors related to the severity of the dolichoectasia also favor ischemia and in some cases are the only factors responsible.

Although our series does not necessarily describe the entire spectrum of ischemic lesions associated with VBD, it nevertheless gives a sufficiently complete view of the possible ischemic complications associated with this pathology.

Selected Abbreviations and Acronyms