Bilateral Vertebral Artery Dissection in a Patient With Afibrinogenemia
Background Afibrinogenemia, a rare coagulation disorder, has not been associated with vertebral artery dissections.
Case Description A 28-year-old woman with afibrinogenemia developed spontaneous neck pain followed by a right medullary infarction, and MR angiography showed extensive bilateral vertebral artery dissection. She was treated with fibrinogen replacement and anticoagulants and showed a favorable evolution, with only mild residual right upper arm incoordination.
Conclusions In this patient spontaneous bilateral vertebral artery dissection complicated afibrinogenemia. Since anticoagulant therapy is usually indicated for arterial dissection, this association created a therapeutic problem. This patient received anticoagulants with fibrinogen replacement, which resulted in a favorable evolution.
Afibrinogenemia, a rare disorder with fewer than 200 cases reported in the literature, is an autosomal recessive disorder with patients often born to consanguineous parents.1 Absence of fibrinogen results in bleeding involving several organs. Neurological complications are infrequent and usually hemorrhagic in origin; however, dissection of cranial arteries has never been reported. We describe a young patient with afibrinogenemia who developed extensive dissection involving both vertebral arteries.
A 28-year-old woman was admitted to our hospital because of right arm clumsiness of sudden onset. She reported moderate neck pain for 1 week and specifically denied prior cervical trauma, strain, or manipulation. On the day of admission she noticed right face numbness, right hand weakness and clumsiness, dysphagia, and tongue deviation to the right. Cranial nerve examination revealed a right Horner's syndrome, slight right peripheral facial nerve paresis, decreased pain and temperature sensation on the right side of the face, right hypoglossal nerve paralysis, and horizontal and rotatory nystagmus on both lateral gazes. There was also marked right arm incoordination and decreased distal joint and vibratory sensations in both right limbs. Pinprick and temperature sensations were impaired in the left extremities, and her gait was unsteady. Physical examination was otherwise unremarkable. Laboratory studies showed prolongation of partial thromboplastin time and prothrombin time and no clot formation. Fibrinogen antigen in plasma was undetectable.
The patient had been diagnosed as having afibrinogenemia, a diagnosis present in one brother. Her parents were first-degree relatives. She took oral contraceptives for 6 months because of polymenorrhea and suffered from occasional mild migraines without aura that were responsive to acetaminophen. No major complications related to afibrinogenemia had been present in the past, and she only needed fibrinogen replacement a few times because of mild bleeding episodes, mainly related to abundant menses. Brain MRI showed a lateral right medullary infarct with small right cerebellar hemisphere ischemic lesions. Foci of hemosiderin deposits were observed over the left frontal cortex consistent with old, subclinical bleeding. T1-weighted images showed signs of bilateral vertebral artery dissection (Fig 1⇓). MR angiography disclosed an extensive arterial dissection involving both vertebral arteries (Fig 2⇓).
Intravenous sodium heparin in continuous perfusion was administered together with cryoprecipitate replacement to maintain the level of fibrinogen at approximately 100 mg/dL. Heparin was maintained for 10 days and then changed to antiplatelet therapy (ticlopidine). She improved, with only persistence of mild right incoordination and face numbness. However, a few days later she again developed increased right arm incoordination and paresis. MR disclosed an occlusion of the right vertebral artery and moderate improvement of the distal stenosis of the left vertebral artery. Eccentric high signal due to methemoglobin was attenuated but still present 1 month after admission. Another course of sodium heparin was administered for 10 days with subsequent improvement and stabilization. Warfarin was substituted 7 days later and was maintained for 3 months, again with fibrinogen replacement. She was left with mild right arm incoordination and has not had any further complications up to the present, more than 1 year later. MR performed 2 months after onset confirmed the occlusion of the right vertebral artery with absence of high signal due to thrombosis maturation. Flow in the left vertebral artery was totally restored.
Arterial dissection occurs when blood enters a vessel wall through an intimal tear and a false lumen of blood is formed within the media.2 The artery most commonly affected is the aorta, followed by the renal and extracranial internal carotid arteries.3
Dissection of the cervical vertebral artery is most often related to sudden mechanical injury of the artery from rotational forces. Most cases have been associated with chiropractic or other neck manipulation, but minor trauma may also result in vertebral artery dissections. Since trivial trauma is in fact a very frequent antecedent, it is dubious whether truly spontaneous cervicocerebral arterial dissections exist. Types of trivial trauma include coughing, sexual activity, and nose blowing, among others. Women are affected 2.5 times more frequently than men. Dissection may affect the artery at any site, but the C1 to C2 level is most frequently involved, suggesting that mechanical factors may play a role even in cases with no apparent history of rotation or injury.4
Extracranial vertebral artery dissection in our patient was not related to cervical trauma. An association of these seemingly spontaneous dissections with cystic medial degeneration, Marfan syndrome, arteritis, fibromuscular dysplasia, and migraine has been reported, although it can occur in microscopically normal arteries.5
An association of vertebral artery dissection to fibrinogen disorder had never been previously reported. It could be speculated that the absence of this critical coagulation molecule could facilitate arterial dissection should an intimal tear occur by preventing clot formation on the vessel wall. A case-control study found oral contraceptives and migraine to be significant risk factors for dissection.6 Both of these factors were present in our patient and could have contributed to dissection. She suffered from mild migraines without aura that responded to acetaminophen and occurred infrequently (approximately one every 1 to 2 months).
Vertebral artery dissection can be detected and monitored by noninvasive vertebral Doppler and MRI in the setting of a clinically suggestive presentation.7 In cases associated with coagulation abnormalities, such as this patient, MR angiography is a particularly important diagnostic tool because it avoids the arterial puncture required for conventional angiography with increased bleeding risk. MRI with conventional axial spin-echo technique can suggest the dissection by demonstrating a high-signal-intensity ring surrounding the narrowed lumen of the vessel representing methemoglobin from subintimal hemorrhage.8 Similar to conventional angiography, in MR angiography the dissected vessel typically appears tapered; however, a high signal from paramagnetic methemoglobin can create an artifactual widening of the lumen on maximum-intensity projection reconstructions from time-of-flight techniques. Because intramural blood appears bright but flow appears dark on spin-echo images, the addition of a spin-echo sequence resolves any confusion.9
Cervicocephalic arterial dissections are usually treated with anticoagulants to prevent the formation of thrombi secondary to the lumen obstruction by the dissection. However, this patient lacked fibrinogen and presented what can be considered a bleeding complication, arterial dissection (ie, hematoma of the arterial media). She was initially treated with heparin for 1 week and then switched to antiplatelet agents with clinical worsening. She improved again with anticoagulant therapy. Whether her worsening and subsequent improvement were related to the change in therapy cannot be determined. Later on, she improved with anticoagulant therapy together with fibrinogen replacement. Because of the lack of prior reports in the literature, we cannot ascertain whether this is the therapy of choice. Further experience with patients with coagulation abnormalities including afibrinogenemia and arterial dissection will be enlightening and necessary to establish its best management.
Reprint requests to Juan C. García-Moncó, MD, Department of Neurology, Hospital de Galdacano, 48960 Galdacano, Vizcaya, Spain. E-mail hospit05@.sarenet.es.
- Received July 9, 1996.
- Revision received August 13, 1996.
- Accepted August 13, 1996.
- Copyright © 1996 by American Heart Association
Gralnick HR. Congenital abnormalities of fibrinogen. In: Williams WJ, Beutler E, Ersley AJ, Lichtman MA, eds. Hematology. New York, NY: McGraw-Hill Publishing Co; 1990:1473-1490.
Mokri B. Dissections of cervicocephalic arteries. In: Meyer FB, ed. Sundt's Occlusive Cerebrovascular Disease. 2nd ed. Philadelphia, Pa: WB Saunders; 1994:45-70.
Schievink WI, Mokri B, Whisnant JP. Internal carotid artery dissection in a community: Rochester, Minnesota, 1987-1992. Stroke. 1993;24:1678-1680.
Saver JL, Easton JD, Hart RG. Dissections and trauma of cervicocerebral arteries. In: Barnett HJM, Mohr JP, Stein BM, Yatsu FM, eds. Stroke: Pathophysiology, Diagnosis and Treatment. New York, NY: Churchill Livingstone, Inc; 1992:671-688.
O'Connell BK, Towfighi J, Brennan RW, Tyler W, Mathews M, Weidner WA, Saul RF. Dissecting aneurysms of head and neck. Neurology. 1985;35:993-997.
Hoffmann M, Sacco RL, Chan S, Mohr JP. Noninvasive detection of vertebral artery dissection. Stroke. 1993;24:815-819.
Nguyen I, Brandt-Zawadzki M, Verghese P, Gillan G. Magnetic resonance angiography of cervicocranial dissection. Stroke. 1993;24:126-131.