Cerebrovasc Dis 2013;35:476-482

Predictors and Timing of Recanalization in Intracranial Carotid Artery and Siphon Dissection: An Ultrasound Follow-up Study

Vicenzini E. · Toscano M. · Maestrini I. · Petolicchio B. · Lenzi G.L. · Di Piero V.
Department of Neurology and Psychiatry, Stroke Unit, Sapienza University of Rome, Rome, Italy
email Corresponding Author


 goto top of outline Key Words

  • Internal carotid artery dissection
  • Intracranial siphon dissection
  • Contrast carotid ultrasound
  • Carotid duplex
  • Anticoagulant therapy
  • Acute ischemic stroke

 goto top of outline Abstract

Background: Intra- and extracranial internal carotid artery dissections (ICD) are two different pathological conditions. Extracranial dissection is considered to be among the most frequent causes of stroke in the young and the segment generally reopens in 2 out of 3 cases, completely or partially, within 6 months. Intracranial ICD (IICD) is considered a rare occurrence in stroke and, accordingly, there are few systematic published data. However, it is a clinically significant condition that may cause severely disabling ischemic stroke or subarachnoid hemorrhage. In the past, sole availability of invasive imaging methods for its detection may have induced an underreporting. The aim of the study was to analyze ultrasound findings, timing and predictors of recanalization in patients with IICD. Methods: IICD acute patients admitted to our Stroke Unit were submitted to carotid sonographic seriated monitoring, daily for the 1st week after symptom onset, at day 14, at month 1 and every 3 months thereafter up to a follow-up of 4 years. Contrast carotid ultrasound was performed in patients with persistent occlusion after month 1. Results: Fourteen acute patients with IICD were enrolled. Extracranial internal carotid patency was observed in 8 patients at first ultrasound scans; all of these showed complete intracranial recanalization within the 1st week and oral anticoagulants were withdrawn after 6 months. Conversely, in 6 patients retrograde extracranial internal carotid thrombosis was immediately observed, since the first ultrasound scans. In 4 of these the occlusion persisted after 4 years while 2 of them had only a partial recanalization, with evidence at contrast ultrasound of still late remodeling processes in the extracranial thrombus up to 2 years after the first observation; for this reason, in these 2 patients anticoagulation was not discontinued, while in the 4 patients with persistent, stable, occlusion, therapy was suspended 1 year after the diagnosis. Conclusions: Identification of the site of dissection - i.e. extra- versus intracranial - is fundamental in clinical studies for outcome and prognosis evaluation. Carotid ultrasound strict surveillance is important to monitor eventual recanalization in patients with ICD, even in a late phase. Retrograde internal carotid thrombosis seems to be correlated with persistent occlusion and partial recanalization. Remodeling of thrombotic material in the internal carotid artery may, however, continue for up to 2 years. In these cases, contrast ultrasound evidence of thrombus morphological changes may support the decision to continue anticoagulation.

Copyright © 2013 S. Karger AG, Basel

goto top of outline Introduction

Intracranial internal carotid artery and siphon dissection (IICD) is considered to be a rare occurrence in stroke and, consequently, there are few systematic published data. However, IICD is a clinically significant condition that may cause severely disabling ischemic stroke or subarachnoid hemorrhage [1]. On the contrary, extracranial ICD is one of the most frequently recognized causes of ischemic stroke in the young, with a prevalence of 10-25% of all ischemic strokes [2]. In the past, the sole availability of invasive imaging methods for IICD detection may possibly have induced an underreporting, but nowadays, with the advances in noninvasive imaging, performed upon specific clinical suspicion in selected cases, the diagnosis appears to be more frequent.

The history of extracranial dissection is generally considered to be highly dynamic in the acute phase, i.e. if the vessel reopens this will happens during the first 3-6 months [3]. Nonetheless, extracranial recanalization may also be observed in the subacute and late phases [4,5]. Local symptoms such as headache, neck pain, pulsatile tinnitus, Horner syndrome or cranial nerve palsy have been described as predictors of complete recanalization [6], while severe internal carotid artery stenosis or occlusion detected in the acute phase reduces the odds of complete vessel reopening [3]. Data on IICD recanalization are less clear, and it seems to carry a worse neurological prognosis than extracranial dissection [1], even though the evidence is still contradictory; a considerably better IICD outcome, even in patients with subarachnoid hemorrhage, has indeed also been reported [7]. Interestingly, there are usually no IICD patients who present with ischemia and who later develop subarachnoid hemorrhage, even among those who receive antithrombotic therapy [1].

Antithrombotic treatment with anticoagulation or antiplatelets is recommended in the acute phase of extracranial dissections to prevent distal embolic ischemic strokes in the ipsilateral middle cerebral artery territory, i.e. the principal pathogenetic cause of cerebral ischemia in these patients [8]. There is, however, no consensus on treatment duration; clinicians usually suspend therapy once the flow in the dissected vessel is soon reestablished and the artery is completely reopened, or when the occlusion results stable after 6 months to 1 year, but without consensus regarding this time [8]. Moreover, there are still controversies on the superiority of warfarin or aspirin in regards to recanalization [9], with only a nonsignificant trend towards higher prevalence of vessel reopening in patients treated with anticoagulants [3]. In ICD, therapeutic options may vary from a medical conservative approach - antiplatelets and anticoagulants - to endovascular procedures [7], but there is still a lack of evidence-based guidelines [10].

The aim of the study is to analyze ultrasound findings during a 4-year follow-up period in 14 patients with IICD, and to describe timing and predictors of recanalization with the related therapeutic implications.


goto top of outline Methods

Seriated carotid duplex scans with high-resolution ultrasound (Siemens Sequoia 513 6L3 linear probe and Siemens S2000 9L4 linear probe), transcranial Doppler (Compumedics DWL MultiDop digital X4) and transcranial color duplex (Siemens Sequoia 512 3V2c probe and Siemens S2000 4P1 probe) were performed in patients admitted to our Stroke Unit for IICD. The diagnosis was performed according to the following criteria: (1) occurrence of acute neurological symptoms and clinical history suggestive of dissection (focal neurological deficit, ipsilateral neck or eye pain, young age, history of cervical neck trauma or exercise stress before symptom onset); (2) absence of internal carotid artery unstable lesions explaining a possible artery-to-artery embolic mechanism; (3) absence of cardiac embolic diseases (arrhythmias, transthoracic and transesophageal echocardiography), and (4) angio-CT or angio-MR imaging of the intracranial vessels, documenting the focal occlusion of intracranial internal carotid artery and/or siphon occlusion with eventual sign of intramural hematoma in the transverse thin layer scans. Extracranial carotid duplex was performed to evaluate the cervical internal carotid artery segment, and transcranial Doppler/transcranial color duplex were used to confirm the absence of flow in the intracranial internal carotid artery or siphon and to evaluate the presence of collateral pathways. In order to exclude a possible embolic pathogenesis of the intracranial occlusion, patients with evidence of unstable carotid plaques, cardiac clots or dissections of the cervical internal carotid artery were not considered.

Ultrasound controls were planned daily for the 1st week, at day 14, at month 1 and every 3 months thereafter. Out-of-schedule control was performed if the patient referred with the occurrence of dissection-related symptoms. After the 1st month, in patients who showed persistence of occlusion with retrograde extracranial internal carotid artery thrombosis, contrast carotid ultrasound (SonoVue 1/2 fl i.v. and real-time CPS real-time contrast software) was performed to evaluate neoangiogenesis in the thrombotic material [11,12,13].

The study was approved by the ethical committee and the procedure did not interfere with the standard and best medical management of these patients.


goto top of outline Results

A total of 14 IICD acute patients (M/F: 9/5; mean age 53.8 ± 6.1 years) were evaluated. Demographic and clinical data are reported in table 1.

Table 1. Demographic features and clinical characteristics of IICD patients

In 8 patients the complete patency of the extracranial internal carotid artery segment at ultrasound, with the typical ‘stop' flow indicative of the distal intracranial occlusion, was observed in the acute phase; in all of these patients the complete recanalization with normalization of blood flow in the extracranial internal carotid artery was observed within the 1st week (fig. 1). At onset, transcranial sonography showed collateral blood flow supply trough the anterior communicating artery that promptly disappeared after siphon reopening.

Fig. 1. Carotid duplex with color (left) and pulsed-wave Doppler (right) in a patient with early recanalization; day 1 (d1), day 4 (d4) and day 7 (d7). Note the complete patency of the tortuous internal carotid artery, the stop flow at day 1 and the recanalization with reappearance of diastolic flow at day 4.

In the other 6 patients early ‘retrograde' extracranial internal carotid thrombosis was instead detected immediately with high-resolution ultrasound and these patients did not present IICD recanalization in the 1st week. A hypoechoic soft mobile material, with a typical aspect of a ‘C'-shaped concave proximal surface towards blood flow - expression of the blood systolic pulse on the fresh thrombus - was observed at the level of the bifurcation (fig. 2) in the cervical internal carotid artery since the first ultrasound scans and, as time elapsed during the 1st month, this hypoechoic material initially showed a homogeneous increase of echogenicity and, after day 15, became heterogeneous and hypo-hyperechoic (fig. 2). In these 6 patients IICD recanalization was not observed and contrast ultrasound was performed at month 1; an intense contrast enhancement in the heterogeneous thrombotic material, index of neovascularization in the highly active remodeling tissue, was detected (fig. 3). In the follow-up, 4 of these 6 patients showed persistence of the occlusion after 4 years, while 2 presented only a partial recanalization at month 3 (fig. 4) and at month 11. In these 2 patients with partial recanalization, contrast ultrasound showed persistence of high-contrast enhancement in the thrombotic material even 2 years after the first diagnosis, with changes also of the morphology, thus indicating still late ongoing remodeling processes. Angio-CT confirmed vessel reopening in these cases, with a residual narrowed internal carotid axis arterial lumen. In the patients with ICA occlusion, the persistence of activated collateral supply through the anterior communicating artery towards the occluded side was observed at transcranial sonography.

Fig. 2. B-mode ultrasound of left internal carotid artery in a patient with persisting occlusion and retrograde extracranial internal carotid artery thrombosis. a Day 1 (d1). b Day 16 (d16). c Month 1 (mo1). Note the changes in the thrombotic material with the increase of echogenicity from day 1 to day 16, with finally marked heterogeneous aspect at month 1 (online suppl. video, Clip 1-3; for all suppl. material, see www.karger.com/doi/10.1159/000350212).

Fig. 3. Power duplex (a) of internal carotid artery retrograde occlusion and contrast carotid ultrasound (b) showing diffusion of the microbubbles in the thrombotic material at month 1 (online suppl. video, Clip 4).

Fig. 4. Color duplex (a), pulsed-wave Doppler (b) and contrast carotid ultrasound (c) of internal carotid artery at month 4 (mo 4) month 8 (mo 8) and month 24 (mo 24) in 1 patient with partial recanalization and persistence of contrast agent diffusion in the thrombotic material, indicative of still ongoing remodeling processes (online suppl. video, Clip 5-10).

Clinically, all patients referred with neck or eye pain at dissection onset, with pain relief 10-15 days after vessel reopening in the 8 patients with complete early recanalization. The other 6 patients with persistent occlusion or late recanalization referred instead inconstantly with a nonspecific pain and only 1 of the 2 patients with late partial recanalization came to our observation out-of-schedule for the occurrence of brief transient visual deficit in the eye ipsilateral to the newly partially reopened artery. Only 1 patient in the group with persistent occlusion resulted in having a severe disabling ischemic stroke, and subarachnoid hemorrhage was observed in none of the patients.

Anticoagulation was withdrawn after 6 months in the 8 patients with complete early recanalization and after 1 year in the 4 patients with persistence of occlusion. In both groups, antiplatelets were introduced at anticoagulant suspension. In the 2 patients showing partial recanalization with evidence at contrast ultrasound of extracranial internal carotid artery thrombus morphological changes and remodeling processes, anticoagulation was instead protracted.


goto top of outline Discussion

In general, clinical studies report three ways of evolution of ICD, with a frequency of one third each: (1) early total recanalization within 3-6 months, (2) early partial recanalization with residual stenosis and (3) chronic (>6 months to 1 year) persistence of occlusion [3]. Nonetheless, cases of late reopening, later than 6 months and up to 2 years, have been described in the literature [4,5]. Factors influencing complete recanalization have been identified, with low odds of recanalization when internal carotid artery stenosis or occlusion is detected in the acute phase [9] and with no clear effects of anticoagulant treatment [3].

The distinction of the site of the dissection, i.e. extra- versus intracranial, is not always clearly reported in clinical studies but, since IICD is generally considered to have a worse outcome than extracranial arterial dissection [1], differentiation between these two different entities is important to correctly define outcome measures and prognosis. Moreover, intracranial dissection is perceived to be rare, and this may be due to possible underreporting in the past, since its recognition required more invasive and sophisticated imaging. Nowadays, advances in noninvasive diagnosis coupled with an increased clinical suspicion may be helpful for its identification, increasing the IICD diagnosis [7].

Histological differences, consisting of a thinner media and adventitia of intracranial vessels as well as their lack of external elastic lamina, may be responsible for intracranial dissection mostly presenting with subarachnoid hemorrhage, contrary to extracranial dissections mostly leading to ischemic and thromboembolic events [7]. Differently from extracranial dissection, which may lead to distal intracranial embolism, intracranial siphon occlusion can also induce a retrograde thrombotic occlusion of the extracranial internal carotid artery; blood flow slows in the extracranial segment of the internal carotid artery, proximal to the occlusion, inducing the activation of coagulation cascade and consequent local cervical segment thrombosis. From a pathophysiological view, when complete retrograde thrombosis in the early phase is observed at level of the extracranial internal carotid artery and the thrombus transforms into a stable organized tissue, vessel reopening may be considered uneven [3].

First of all, in our small cohort of IICD patients, none of the patients presented with subarachnoid hemorrhage; this may be related to a bias in the selection of ischemic stroke patients to be addressed to the Stroke Unit, while those with subarachnoid hemorrhage are usually admitted to neurosurgery units. In all those patients in whom the extracranial segment of the internal carotid artery was completely patent in the acute phase, early complete vessel reopening within the 1st week was observed. On the contrary, those in whom the extracranial segment showed early signs of retrograde thrombosis did not present early recanalization. Only 2 of the latter developed late thrombus remodeling processes that led to partial recanalization. Even though our small numbers do not allow making statistical calculations, acute detection of retrograde thrombosis in the cervical internal carotid artery segment appears to be an important negative predictor in the early phase in regards to the intracranial vessel reopening. Moreover, this typical C-shaped concave surface of the thrombosis - not yet described in the literature - is also an important sign, allowing differentiation from an occluding thrombus migrating from the heart (generally characterized by a hyperechoic head with a C-shaped convex surface towards the flow and a hypoechoic tail), since it may be the result of the blood systolic drive in the central part of the fresh retrograde thrombus [14,15].

Contrast-enhanced ultrasound is a reliable tool to identify neoangiogenesis and remodeling in carotid artery plaques [11,12]. In our patients, the follow-up of internal carotid artery retrograde thrombosis showed with this approach that not only the vessel may unevenly reopen after complete occlusion, but also that thrombus remodeling can still be visible up to 2 years from the first event. This datum may raise discussion about which should be considered the most appropriate therapeutic strategy; anticoagulation may impair healing of the intramural hematoma, antiplatelets may have higher recanalization rates [8], statins have a pleiotropic effect that may reduce angiogenesis, and intravascular approach is becoming feasible in specialized centers [7]. Being that surgical procedures were not indicated in our patients with late partial recanalization, the changes observed over time and the neoangiogenesis detected in the thrombus texture suggested that the thrombotic material, with the distal segment being patent, could be at high risk of distal embolism. Thus, the continuation of anticoagulant therapy may be more indicated, probably helping also in the vessel reopening as well as preventing distal embolism from the still active remodeling thrombus. The positive effects of anticoagulant therapy may have been also suggested in another case with bilateral IICD reported from our group [5], where anticoagulation prevented contralateral internal carotid artery complete occlusion in favor of an early recanalization during the second IICD and induced a very late recanalization of the former occluded vessel. Moreover, it has to be borne in mind that the timing of intracranial vessel reopening is considered important to improve overall clinical outcomes [16].

In conclusion, when considering ICD, the site of vessel damage, i.e. intra- or extracranial, has to be clearly identified and reported. Carotid ultrasound surveillance is important to monitor eventual recanalization in IICD patients, even in a late phase. Retrograde internal carotid thrombosis appears to be correlated with persistent occlusion and partial recanalization. Remodeling of thrombotic material in the internal carotid artery may however continue up to 2 years. In these cases, contrast ultrasound evidence of thrombus morphological changes and still ongoing remodeling processes may be supportive for anticoagulation continuation.


goto top of outline Disclosure Statement

The authors declare that they have no conflicts of interest. No funding was received for this study.

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    External Resources

  16. Cho KH, Lee DH, Kwon SU, Choi CG, Kim SJ, Suh DC, Kim JS, Kang DW: Factors and outcomes associated with recanalization timing after thrombolysis. Cerebrovasc Dis 2012;33:255-261.

 goto top of outline Author Contacts

Edoardo Vicenzini, MD, PhD
Department of Neurology and Psychiatry
Sapienza University of Rome
Viale dell'Università 30, IT-00185 Rome (Italy)
E-Mail edoardo.vicenzini@uniroma1.it

 goto top of outline Article Information

Received: November 20, 2012
Accepted: February 25, 2013
Published online: May 31, 2013
Number of Print Pages : 7
Number of Figures : 4, Number of Tables : 1, Number of References : 16
Additional supplementary material is available online - Number of Parts : 11

 goto top of outline Publication Details

Cerebrovascular Diseases

Vol. 35, No. 5, Year 2013 (Cover Date: June 2013)

Journal Editor: Hennerici M.G. (Mannheim)
ISSN: 1015-9770 (Print), eISSN: 1421-9786 (Online)

For additional information: http://www.karger.com/CED

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