Dissection of All Four Cervical Arteries in a Patient with Fibromuscular Dysplasia – a Case Report

Summary

We describe a rare case of a woman, in whom dissection of both carotides, as well as both vertebral arteries occurred in the period between 2005 and 2015 (for the first time at the age of 32 years). Occlusive dissection developed in all occasions except the right internal carotid artery that was treated with angioplasty and stenting. In spite of this, the patient developed no cerebral lesion and neurological deficit remained limited to the left-side Horner syndrome due to a damage of the cervical sympathetic trunk. Digital subtraction angiography revealed alternating segments of stenoses and aneurysmal dilatation of arteries, i.e. changes typical for fibromuscular dysplasia. Affection of neither renal, nor coronary bloodstream was proven in the patient. The case report demonstrates well the wide variability of clinical manifestations of cervical artery dissections.

Key words:
dissection – carotid artery – vertebral artery – diagnostics – treatment – fibromuscular dysplasia

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

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Chinese summary - 摘要

在纤维肌性发育不良区域中四个颈动脉的解剖 - 病例报告

我们将描述一个罕见的女性病例，在2005年至2015年期间，进行了两侧颈动脉以及两侧椎动脉解剖（第一次是在32岁）。除了使用血管成形术和支架治疗的右颈内动脉之外，其还包括一个闭塞性解剖。尽管如此，患者没有形成脑损伤，并且神经功能缺陷仍限制于由于颈交感神经干损伤引起的左侧霍纳综合征。数字减影血管造影显示了交替的狭窄和动脉瘤样扩张动脉段，即典型的肌纤维发育不良。 对患者的肾脏和冠状动脉血流的影响都没有被证实。 该病例报告显示颈动脉解剖的临床表现变化很大。

关键词：

解剖 - 颈动脉 - 椎动脉 - 诊断 - 治疗 - 肌纤维发育不良

Introduction

Dissection of cervical arteries is a frequent cause of cerebral ischemia in younger patients (up to 25% at the age of < 45) [1,2]. Contrary to the usually considered traumatic etiology, spontaneous occurrence prevails (60%) [3], often in the terrain of fibromuscular dysplasia (FMD). The annual incidence rate is 3-5/100,000 [1,2]. However, it is expected that this disease is underdiagnosed due to its extremely variable course – from asymptomatic course to severe stroke.

We describe a rare case of a woman, in whom dissection of both carotid, as well as both vertebral arteries (VAs) occurred during the years 2005–2015.

Case report

In April 2005 (at the age of 32 years), a female patient developed an intensive retroauricular pain on the right side with a non-systematic instability in space and temporary dysphagia. These problems occurred two days after the mobilization treatment of cervicocranical syndrome. Magnetic resonance angiography (MRA) revealed the dissection of the right VA with its occlusion by expanding thrombus. No ischemia of the brain tissue was detected and objective neurological finding was normal. The patient was treated by the anticoagulation therapy – Fraxiparine (Aspen, Notre Dame de Bondeville, France) was given subcutaneously twice a day in a 0.6 ml dose and after two weeks she was switched to Warfarin (Orion Corporation, Espoo, Finland) 7.5 mg/day for a period of two months. MRA performed after two months showed partial recanalization of the artery.

In April 2006, due to the history of one month lasting pain in the left back region of the neck spreading to the head and a temporary left side hypoacusis, repeated MRA examination was performed proving the occlusion of the left VA from C2 to foramen magnum with a well established collateral circulation (intracranial flow was normal).

In April 2015, the patient woke up at night due to a severe pain in the left mandible and, she noticed a dropped left upper eyelid. The objective finding revealed a Horner syndrome on the left side and, computed tomography angiography (CTA) showed the dissection of the left internal carotid artery (ICA) with its occlusion. The patient received a dual antiplatelet medication – Godasal (PRO.MED.CS Praha a.s., Prague, Czech Republic) 100 mg/day and Trombex (Sanofi Winthrop Industrie S.A., Ambarés, France) 75 mg/day – and a preventive dose of Fraxiparine (0.4 ml once a day). Two days later, the digital subtraction angiography (DSA) confirmed the occlusion of the left ICA (Fig. 1) and the commencing dissection of the right ICA (Fig. 2) Signs of FMD were present in all four cervical arteries (Fig. 3). On the next day, an 80% stenosis of the right ICA was detected using the MRA and treated acutely on the same day by the percutaneous transluminal angioplasty and stenting (PTAS) with the insertion of the stent Leo 5.5 × 50 mm (Balt, Montmorency, France) (Fig. 4). During the whole hospitalization, the patient showed no clinical symptoms of a cerebral lesion, which was not even detected by magnetic resonance imaging. The affection of the left cervical sympathetic trunk persisted at discharge. Screening examination of renal and coronary arteries did not prove FMD outside the cerebral vessels.

Discussion

In the case of the arterial dissection, a rupture of the intima with intramural bleeding occurs with the subsequent coagulum formation within the vessel wall. A possible ischemia of a supplied organ is caused either by a hemodynamic mechanism due to the severe stenosis or occlusion of an affected cervical artery, or more frequently by a distal embolization of the thrombus [4]. The pathogenesis of dissection is not known in a majority of cases and its etiology is usually classified as spontaneous or traumatic. A risk of chiropractic interventions is being often discussed. Despite the fact that our patient also underwent manipulative therapy of the cervical spine before affection of the right VA, the mechanical injury is proved only in a minority of cases both in patient history and histologically [2,5]. The definition of a mechanical injury is also questionable, it is certainly possible to accept the association with the cervical spine injury, however, on the contrary, the frequent association of dissection with the preceding infection [6] cannot be explained merely by an excessive stress of the vascular wall during coughing, or sneezing, as such a stress represents a common part of life and the healthy vessels must endure it without any consequences. Therefore, the etiopathogenesis is more complex and includes pre-existing affection of the blood vessel, for example in arteritis, or hyperhomocysteinemia (unlike atherosclerosis, the association of the higher occurrence of dissection with hyperhomocysteinemia due to the mutation of the gene for methylenetetrahydrofolate reductase (MTHFR) was proven [7]), however an inborn, or acquired defect of connective tissues (e.g., Ehlers-Danlos syndrome, or FMD, which was detected also in the case of our patient) is more significant.

The diagnosis of arterial dissection does not usually cause problems, provided that symptomatic cerebral ischemia develops. In the case of carotid affection, the most frequent symptoms include contralateral hemiparesis and/or hemihypoesthesia, or dysphasia.  Amaurosis fugax represents a possible, but less frequent symptom. A detailed examination of the cerebral tissue and arterial supply is subsequently a routine part of stroke diagnostics. 

The situation is more complicated, if dissection does not lead to the development of symptomatic cerebral ischemia. Neck pain with its propagation to the jaw or occiput, in the case of carotid artery affection possibly accompanied by the Horner syndrome, represent typical, unfortunately completely non-specific symptoms. Moreover, VA dissection is associated with even less specific symptoms. Occipital pain sometimes perfectly imitates the cervicocranial syndrome and, possible vertigo due to microembolization to cerebellar arteries does not have to necessarily exceed the clinical picture of the mentioned benign cause. An insignificant local finding, i.e., the absence of cervical pain may be helpful in the diagnostic process. In the case of doubts, a neuroradiological examination is indicated. DSA represents the “gold standard”, however, not the first choice method due to its invasive nature and expensiveness. Ultrasound (US) is a non-invasive method with a high sensitivity (75–95%) in the case of carotid artery dissection [8], however, with the less specific finding in the case of the arterial occlusion or distal localization of the dissection. Computed tomography angiography has a higher sensitivity and specificity and also good availability. Nevertheless, its use is associated with a higher radiation load, especially with respect to the fact that dissection is being suspected often in younger patients. Therefore, in the case of suspected arterial dissection, the use of MRA appears to be optimal. Despite its higher cost, it combines the advantages of other diagnostic methods – it is almost non-invasive, sufficiently sensitive and specific, enables also the display of intracranial circulation and has no radiation load. Nevertheless, it is not possible to extensively examine all patients, coming every day to the out-patient department with cervical back pain, or various vague complaints and, unfortunately, no algorithm is available which would make it possible to easily and quickly select the patients, in whom the performance of a costly or exposing radiodiagnostics would be justified. Therefore, physician experience is necessary. In the case of our patient, the occlusive dissection of the right VA was diagnosed by the MRA and it was also well visible during the follow-up US examination. The chronic occlusion of the left VA was also detected by the MRA, while the US examination performed two days earlier was falsely negative. Dissection of the left ICA was detected by the CTA and, dissection of the right ICA was revealed by the DSA performed two days later. However, in this case, the different finding was more like caused by the rapid dynamics of the disease.

Treatment of the dissection is based specially on the prevention of distal embolization [9,10]. In the case of our patient, the treatment corresponds with its historical development. The formerly preferred long-term anticoagulation therapy was almost abandoned, as no significant difference was found between the efficacy of the anticoagulation and antiplatelet therapy [11–13], while the anticoagulation therapy is associated with a higher risk of hemorrhagic complications. PTAS may be considered in the case of a rapid development of stenosis with a hemodynamic mechanism of cerebral ischemia, in the case of a threatening occlusion or in patients with stroke or transient ischemic attack and extracranial carotid or vertebral arterial dissection who have definite recurrent cerebral ischemic events despite medical therapy [9]. This is why our patient was administered a dual antiplatelet therapy in advance; a low dose of the low-molecular-weight heparin was used only as prevention of thromboembolism. No strict guideline exists regarding the indication of endovascular therapy and its possible indication depends on a specific situation, especially on the speed of development of stenosis and its localization.

DSA revealed also FMD in our patient. This is a disease, in which an artery is deformed due to the abnormal development of its wall, possibly resulting in the development of stenosis, formation of aneurysms, or both. The abnormal vascular wall is more vulnerable and this typical pre-exposing factor may lead to the occurrence of dissection, both spontaneously of following a minor mechanical insult. Renal and cerebral arteries are affected most frequently [14]. Despite the fact that the disease was described already in 1938 [15], its cause is not known yet, but it is likely a congenital disease, as approximately 10 % of patients have an affected relative. However, it is not possible to monitor FMD penetration in the family of the affected individuals using solely the clinical examination, as this disease remains often asymptomatic. In one study, the phenotype was assessed according to evaluation of the affection of connective tissues obtained by a skin biopsy. A pedigree of three families suggested an autosomal dominant inheritance pattern, however, no specific gene mutation was determined and the locus is probably heterogeneous [16]. Up to 6 % of the population may be affected [17]. In the long-term study, in which renal angiography was performed in healthy kidney donors, there was an abnormal finding in 3.8 % [18]. However, the disease incidence is higher, as, similarly as in our patient, isolated affection occurs also in other than renal arteries.

The FMD classification is not unified. In the case of the affection of renal arteries, it is possible to divide the disease into four groups [19]. 1) Medial fibroplasia, the most frequent type characterized by formation of aneurysms with a diameter exceeding the lumen of the artery and by benign, usually asymptomatic course. 2) Perimedial fibroplasia, for which the formation of aneurysms is also typical, however, their size does exceed the lumen of an affected artery; the progression is usually faster, but, fortunately, endovascular treatment is effective. 3) Medial hyperplasia is characterized by a smooth delimitation of stenosis; this type can be also well treated by angioplasty. 4) Intimal fibroplasia is characterized by short smooth stenoses, which cannot be dilated using the angioplasty. In our patient, the DSA finding is mostly resembling the medial fibroplasia. It also corresponds with its benign course. Unfortunately, the patient has not appeared yet for the planned biopsy, which would enable verification of the affection.

Conclusion

Dissection of cerebral arteries represents the most frequent cause of cerebral ischemia in young patients. However, the affection of the artery can have a benign, or completely asymptomatic course even despite potential development of the occlusion. On the other hand, the diagnosis is more difficult in these cases, as it is not possible to easily differentiate a large group of patients with cervicogenic pain and various vague complaints. Although it is not always possible to determine the cause of dissection, there is a frequent association with the inborn connective tissue diseases, such as FMD in the case of our patient. Potential organ complications occur either on the basis of microembolization, or through a hemodynamic mechanism due to arterial stenosis or occlusion. The risk of embolization can be reduced by the anticoagulation or antiplatelet therapy, however, the progressing stenosis can only be treated by PTAS.