Pseudoxanthoma elasticum

Cervicocephalic arterial dissections (CCAD) are an increasingly recognized cause of ischemic stroke in young adults. Various treatments have been suggested but no controlled trial has ever been performed. Medical treatment has included anticoagulant or platelet antiaggregant therapy. Surgical correction has been proposed for selected patients who have failed medical therapy. Percutaneous balloon angioplasty and stenting have been increasingly used in some patients, although long-term results are unknown. The objective of the study was to review our recent experience with the management and outcome of extracranial CCAD. We identified 27 patients with extracranial CCAD who were evaluated, treated and/or followed by our Stroke Service from September 1995 to August 2001. Clinical presentation, diagnostic evaluation, management, and outcome were reviewed. There were 15 men (56%) and 12 women (44%) with mean ages of 38 and 43 years respectively. Diagnosis was made by cerebral angiography in 15 (56%) patients and by MRI/MRA only in 12 (44%) patients. Twenty-two patients had spontaneous and five had traumatic extracranial CCAD. Most common associated disorders were arterial hypertension (37%) and migraine (26%). One patient presented only with a painful post-ganglionic Homer syndrome, another patient with neck pain and post-ganglionic Homer syndrome, another patient solely with protracted unilateral headaches, three with transient ischemic attacks (TIA), and 21 with ischemic strokes. The internal carotid artery (ICA) was the most frequently involved vessel (63%), followed by the vertebral artery (30%), and multivessel involvement in two patients (7%). Eighteen patients received anticoagulant therapy and nine platelet anti-aggregants. Follow-up extended from 2 to 115 months, with a mean of 58 months. At the end of follow-up, 23 (85%) patients had either no disability or only minor sequelae (modified Rankin score: 0 to 1), and four (15%) patients had moderate limitations (modified Rankin score: 2 to 3). Two patients had a recurrent ischemic stroke, one unrelated to recurrent CCAD, and the other following percutaneous balloon angioplasty/stenting for treatment of a persistent vertebral artery pseudoaneurysm. Most CCAD involved the extracranial ICA. The clinical presentation is variable, most patients having an ischemic stroke or TIAs. The short- and long-term outcome are usually favorable with either anticoagulant or platelet antiaggregant therapy. A medical initial approach to the management of extracranial CCAD is recommended for most patients. [Neurol Res 2002; 24: 395-398]

Keywords: Cervicocephalic arterial dissections; ischemic stroke; early diagnosis; clinical evaluation

INTRODUCTION

Cervicocephalic arterial dissections (CCAD) are a wellrecognized cause of ischemic stroke. CCAD are one of the most common nonatherosclerotic causes of stroke in young adults and can occasionally result in devastating neurologic sequelae1-4. Recent reports suggest an average annual incidence of 2.5 to 3.0/100,000 patients5. CCAD are produced by subintimal penetration of blood through an intimal tear or hemorrhage of the vasa vasorum of the media with subsequent longitudinal extension of the intraluminal hematoma between its layers. These abnormalities can cause vessel narrowing that may progress to complete occlusion (subintimal dissection), aneurysm formation (subadventitial dissection) or both6. A false lumen appears if the blood reenters the true lumen. Spontaneous CCAD are not infrequent8,9. The first case of spontaneous ICA dissection was reported in 1954(10); subsequent cases were reported sporadically11-20.

Early diagnosis is crucial for the initiation of appropriate treatment and monitoring potential complications. Treatment has traditionally included anticoagulant therapy, platelet anti-aggregant therapy, or surgery. However, there is still controversy concerning the optimal therapy for patients with CCAD. In this report, we described our recent experience with the clinical presentations, management, and outcome of patients with extracranial CCAD evaluated at Indiana University Medical Center by our Stroke Service.

SUBJECTS AND METHODS

We identified all patients from our outpatient and inpatient log books, who were diagnosed with extracranial CCAD and examined, either at the initial presentation or follow-up after dissection in the Outpatient Clinic by members of the Stroke Service at Indiana University Medical Center from September 1995 to August 2001. We reviewed the clinical presentations, diagnostic methods, treatments, complications and outcome. The modified Rankin score was determined during the latest follow-up evaluation.

RESULTS

We identified 27 patients with CCAD. Fifteen were men (56%) and 12 were women (44%) with mean ages of 38 and 43 years respectively. Diagnosis was made by cerebral angiography in 15 patients, and by MRI/MRA in 12 patients. Twenty-two (81%) patients had spontaneous and five (19%) had traumatic CCAD. Among patients with traumatic CCAD, three were involved in a motor vehicle accident with carotid artery dissection and two experienced a vertebral artery dissection following chiropractic manipulation. Most common associated disorders were arterial hypertension (37%), migraine (26%) and cigarette smoking (19%) (Table 1). In regards to the clinical presentation, 21 (77%) patients had ischemic territorial infarcts, three (11%) had transient ischemic attacks, one (4%) presented only with a painful post-ganglionic Horner syndrome, one (4%) had neck pain and post-ganglionic Horner syndrome, and one (4%) had only a protracted unilateral headaches.

The extracranial internal carotid artery (ICA) was involved in 17 (63%) patients, while the extracranial vertebral artery in eight (30%) patients. Multivessel involvement was present in two (7%) patients. Both of these latter patients had bilateral ICA dissections, one spontaneous and the other one traumatic. None of our patients had underlying fibromuscular dysplasia or other obvious predisposing arteriopathy as detected by ancillary imaging techniques. Three patients had extracranial pseudoaneurysms; two involved the vertebral artery and one the ICA. Only one of these pseudoaneurysms was associated with a traumatic dissection. Eighteen patients received anticoagulant therapy, and nine patients were treated with platelet anti-aggregants.

Follow-up extended from two to 115 months, with a mean of 58 months. At the end of follow-up, 23 (85%) patients had either no disability or only minor sequelae with a modified Rankin score 0 to 1, and four (15%) patients had moderate limitations with a the modified Rankin score 2 to 3. These four patients had extracranial ICA dissections, three spontaneous and traumatic.

Two patients had recurrent ischemic strokes during follow-up. One patient experienced an ischemic stroke without recurrent CCAD 14 months after his presenting ischemic stroke with unfavorable outcome. The other patient had a minor stroke following a percutaneous balloon angioplasty/stenting (not recommended by us) for treatment of a persistent extracranial vertebral artery pseudoaneurysm with a good outcome. There were no fatalities.

DISCUSSION

Spontaneous CCAD account for 2% of all ischemic strokes, but may be more common than previously appreciated, especially among young and middle aged patients21. This is most likely attributable to improved diagnosis through the use of modern neuroimaging techniques and heightened clinical awareness of its diverse clinical spectrum.

CCAD may cause transient retinal, hemispheric, or posterior fossa ischemia, painful Horner syndrome, ischemic optic neuropathy, central retinal artery occlusion, ophthalmic artery occlusion, visual scintillations associated with choroidal hypoperfusion, hemicranial pain, scalp tenderness, isolated or multiple cranial nerve palsies, pulsatile tinnitus, subjective bruit or subarachnoid hemorrhage especially in cases of intracranial arterial dissection. Major presenting features of extracranial ICA dissection are ischemic strokes or transient ischemic attacks associated with ipsilateral neck, facial, orbital, or head pain. Dissection of the extracranial vertebral artery is often characterized by sudden onset of pain, frequently severe and localized to the posterior aspect of the neck or head, followed by progressive onset of posterior fossa ischemic symptoms3,7.

Cerebral infarction is reported in approximately 80% of patients with CCAD and TIA in 20%-30%8. In our patients, 77% had ischemic stroke, and 11% had TIAs. Fourteen patients (52%) had headache at onset, in one patient the only symptom.

Several explanations have been proposed for ischemic symptoms resulting from CCAD. Most are thought to result from embolism or hemodynamic compromise22-24. Several predisposing factors for CCAD have been identified, including Marfan syndrome, type IV Ehlers-Danlos, cystic medial necrosis, pseudoxanthoma elasticum, alpha-1 antitripsin deficiency, fibromuscular dysplasia, and arterial coils. None of these conditions were present in our patients. Established stroke risk factors are infrequent and present only in a minority of patients with CCAD11,25.

Cerebral angiography has generally been considered until recently the diagnostic gold standard for CCAD, but is an invasive procedure with potential risk for complications26. Noninvasive vascular imagine techniques with ultrasonography20,24,25,27-29, CT3,24,29, and combined MRI and extracranial and intracranial MRA3,24,29-34 are increasingly utilized as reliable methods for establishing the initial diagnosis of CCAD without exposing the patient to the risks of arteriography, and permit serial monitoring of lesion evolution. MRI has a sensitivity of 84% and a specificity of 99% for the diagnosis of ICA dissection, while MRA is reported to have a sensitivity of 95% and a specificity of 99%32.

Due to the lack of randomized clinical trials, the optimal management of CCAD remains controversial. Several medical treatments, including anticoagulants18,21,35, platelets antiaggregants, surgical36 and endovascular procedures37,38 have been proposed. Various surgical procedures have also been described, including ligation, trapping, removal of intramural hematoma, arterial resection with vein graft replacement, gradual intraluminal dilation, surgical occlusion of distal extracranial ICA, superficial temporal arterymiddle cerebral artery bypass, and most recently percutaneous balloon angioplasty and stenting11,12,37-39 However, multiple studies have documented the frequent spontaneous resolution of arterial dissection9,40,41. Most recanalizations occur within three months, but can occur as early as seven days after diagnosis. While the use of anticoagulation might seem contra-indicated in a disorder defined by hemorrhage into the arterial wall, cerebral ischemia often results from secondary thromboembolic complications. Therefore, early anticoagulation with intravenous unfractionated heparin followed by a 3-6 months course of warfarin (target INR = 2.0-3.0), is often recommended1,12,18,23,25,35. However, most of these studies involved small numbers of patients, and in some the duration and nature of treatment were not specified.

Eighteen of our patients were treated with anticoagulants and nine with platelet anti-aggregants. The rationale behind the choice of treatment was not clear in the patients that were initially treated in other institutions. All patients diagnosed with CCAD in our institution received anticoagulant therapy for a period of six months, except one who was treated with a platelet antiaggregant as the dissected vessel was already occluded.

Our preliminary results confirm an excellent shortand long-term outcome for most patients with extracranial CCAD treated medically with either anticoagulant therapy or platelet antiaggregants. A medical approach to the initial management of extracranial CCAD is therefore recommended for most patients.

REFERENCES

1 Biller J, Hingtgen WL, Adams HP Jr, Smoker WRK, Goderky JC, Toffol GJ. Cervicocecephalic arterial dissections. A ten-year experience. Arch Neurol 1986; 43: 1234-1238

2 Steinke W, Rautenberg W, Scharwt A, Hennerici M. Noninvasive monitoring of internal carotid artery dissection. Stroke 1994; 25: 998-1005

3 Provenzale JM, Morgenlander JC, Gress D. Spontaneous vertebral dissection: Clinical, conventional angiographic, CT and MR] findings. J Comput Assist Tomogr 1996; 20: 185-193

4 Schievink WI, Mokri B, Piepgras DG. Spontaneous dissections of cervicocephalic arteries in childhood and adolescence. Neurology 1994; 44: 1607-1612

5 Giroud M, Fayolle H, Andre N, et al. Incidence of internal carotid artery dissection in the community of Dijon. J Neurol Neurosurg Psychiatry 1994; 57: 1443 (letter)

6 Guillon B, Levy C, Bousser MG. Internal carotid artery dissection: An update. J Neurol Sci 1998; 153: 146-158

7 Fisher CH, Ojeman RG, Roberson GH. Spontaneous dissection of cervico-cerebral arteries. Can J Neurol Sci 1978; 5: 9-19

8 Schievink WI, Mokri B, O'Fallon WM. Recurrent spontaneous cervical arterial dissection. N Engl J Med 1994; 330: 393-397

9 Schievink WI, Mokri B Piegras D. Angiographic frequency of sacular intracranial aneurysm in patients with spontaneous cervical arterial dissection. J Neurosurg 1992; 76: 62-66

10 Jentzer A. Dissecting aneurysm of the left carotid artery. Angiology 1954; 5: 232-234

11 Bradac GB, Kaernbach A, Bolk-Weischedel D, et al. Spontaneous dissecting aneurysm of cervical cerebral arteries: Report of six cases and review of literature. Neuroradiology 1981; 21: 149-154

12 Ehrenfeld WK, Wylie EJ. Spontaneous dissection of the internal carotid artery. Arch Surg 1976; 111: 1294-1300

13 Fisher CM. The headache and pain of spontaneous carotid dissection. Headache 1982; 22: 60-65

14 Fisher CM, Ojemann RG, Robertson GH. Spontaneous dissection of cervico-cerebral arteries. Can J Neurol Sci 1978; 5: 9-19

15 Friedman WA, Day AL, Quisling RG, et aL Cervical carotid dissecting aneurysms. Neurosurgery 1980; 7: 207-213

16 Gee W, Kaupp HA, McDonald KM, et aL Spontaneous dissection of internal carotid arteries: Spontaneous resolution documented by serial ocular pneumoplethysmography and angiography. Arch Surg 1980; 115:944-949

17 Kapp JP, Smith RR. Spontaneous resolution of occlusive lesions of the carotid artery. J Neurosurg 1982; 56: 73-79

18 McNeill DH Jr, Dreisbach J, Marsden RJ. Spontaneous dissection of the internal carotid artery: Its conservative management with heparin sodium. Arch Neurol 1980; 37: 54-55

19 Mokri B, Sundt TM Jr, Houser OW, Piegrass DG. Outcome in spontaneous dissections of the internal carotid arteries. Abstract. Ann Neurol 1982; 12: 75

20 Rawat B, Gerroti M, Asnby P, Simons M. Application of duplex Doppler sonography in intracranial carotid dissection. J Ultrasound Med 1992; 11: 121-123

21 Schievink Wl. Spontaneous dissection of the carotid and vertebral arteries. N Engl J Med 2001; 344: 898-906

22 Pozzati E, Giuliani G, Acciarri N, et al. Long-tern follow-up of occlusive cervical carotid dissection. Stroke 1990; 21: 528-531 23 Bogousslavsky J, Regli F, Despland PA. Spontaneous carotid

dissection with acute stroke. Arch Neurol 1987; 44: 137

24 Mullges W, Ringelstein EB, Leibold M. Non-invasive diagnosis of internal carotid artery - new diagnosis and pathogenic aspects. Forst Neurol Psychiatr 1991; 59: 12

25 Sturzenegger M. Ultrasound findings in spontaneous carotid artery dissection: The value of duplex sonography. Arch Neurol 1991; 48: 1057-1063

26 De Bray JM, Lhoste P, Dubas F, Emile J, Saumet JL. Ultrasonic features of extracranial carotid dissections: 47 cases studied by angiography. J Ultrasound Med 1994; 13: 659-664

27 Mullges W, Ringelstein EB, Leibold M. Non-invasive diagnosis of internal carotid artery dissections. J Neurol Neurosurg Psychiatry 1992; 55: 98-104

28 Eljamel MSM, Humphrey PRD, Shaw MDM. Dissection of the cervical internal carotid artery: The role of Doppler duplex studies and conservative management. J Neurol Neurosurg Psychiatry 1990; 53:379-383

29 Zuber M, Meary E, Meder J-F, Mas J-L. Magnetic resonance imaging and dynamic CT scan in cervical dissections. Stroke 1994; 25: 576-581

30 Stringaris K, Liberopulus K, Giaka E, Kokkinis K, Bastounis E, et al. Three-dimensional time-of-flight MR angiography and MR imaging versus conventional angiography in carotid artery dissections. Int Angiol 1996; 15: 20-25

31 Jacobs A, Lanfermann H, Szelies B, Schroder R, Neveling M. MRI and MRI-guided therapy of carotid and vertebral artery dissections. Cerebrovasc Dis 1996; 6(Suppl.2): 80

32 Levy C, Laissey JP, Raveau V, Amarenco P, Servios V, Bousser MG, Tubiana JM. Carotid and vertebral artery dissections: Threedimensional time-of-flight MR angiography and MR imaging vs conventional angiography. Radiology 1986; 158: 157-161

33 Klufas Ra, Hsu L, Barnes PD, Patel MR, Schwartz RB. Dissection of the carotid and vertebral arteries: Imaging with MR angiography. Am J Roentgenol 1995; 164: 673-677

34 Sue DE, Brant-Zawadzki MN, Chance). Dissection of cranial arteries in the neck: Correlation of MRI and arteriography. Neuroradiology 1992; 34: 273-278

35 Chapleau CE, Robertson JT. Spontaneous cervical carotid dissection: Outpatient treatment with continuous heparin infusion using a totally implantable infusion device. Neurosurgery 1981; 8: 83-87

36 Hardin CA, Snodgrass RG. Dissecting aneurysm of internal carotid artery treated by fenestration and graft. Surgery 1964; 55: 207-209

37 Liu AY, Paulsen RD, Marcellus ML, et al. Long-term outcomes after carotid stent placement for treatment of carotid artery dissection. Neurosurgery 1999; 45: 1368-1374

38 Bejjani GK, Monsein LH, Laird JR, et al. Treatment of symptomatic cervical carotid dissections with endovascular stents. Neurosurgery 1999; 44:755-761

39 O'Dwyer JA, Moscow N, Trevor R, et al. Spontaneous dissection of the carotid artery. Radiology 1980; 137: 379-385

40 Pozzati E, Giuliani G, Acciarri N, et al. Long-term follow-up of occlusive cervical carotid dissection. Stroke 1990; 21: 528-531 41 Pozzati E, Giuliani G, Poppi M, et al. Blunt traumatic carotid

dissection with delayed symptoms. Stroke 1989; 20: 412-416

Fernando Gonzales-Portillo*, Askiel Bruno^ and Jose Biller^

*Department of Neurology, The University of Arizona Health Sciences Center, Tucson, AZ ^Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA

Correspondence and reprint requests to: Fernando Gonzales-Portillo, Department of Neurology, University of Arizona Health Sciences, 1501 N. Campbell Ave., PO 245023, Tucson, AZ 85724-5023, USA.

Accepted for publication March 2002.

Copyright Forefront Publishing Group Jun 2002
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