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DURAL SINUS THROMBOSIS ENDOVASCULAR THERAPY Frank P. K. Hsu, MD, PhD, Todd Kuether, MD, Gary Nesbit, MD, and Stanley L. Barnwell, MD, PhD

Dural sinus thrombosis (DST) is a term that encompasses thrombosis of cortical and deep cerebral veins and the dural sinuses. The thrombosis of the cerebral venous system prevents normal drainage of blood and thus causes venous hypertension, increased intracranial pressure, and subsequent hemorrhagic infarction. Because it is a relatively rare problem and its presentation is often nonspecific, the diagnosis is frequently delayed or missed. Although there is a lack of true incidence and prevalence data, it is agreed that with the advent of better diagnostic tools, the diagnosis is made with increasing frequency. Antithrombotic agents and systemic thrombolytic agents have been used with variable success. Recent advances in endovascular techniques allow local infusion of thrombolytic agents in the treatment of DST with success. VENOUS ANATOMY

The cerebral venous system is composed of three distinct parts: the superficial cerebral veins, the deep Galenic system, and the dural sinuses. The dural sinuses collectively drain both the cortical veins and the deep Galenic system. The dural sinuses then, in turn, drain into the internal jugular veins. The dural sinuses include the superior sagittal, inferior sagittal, cavernous, straight, superior and inferior, petrosal, transverse (also

From the Department of Neurological Surgery, Dotter Interventional Institute, Oregon Health Sciences University, Portland, Oregon





known as lateral), and sigmoid sinuses. The dural venous sinuses carry venous blood in channels formed by splits in the dura mater over the cerebral convexity, in the falx, and in the cerebellar tentorium. The superior sagittal sinus plays a critical role in venous outflow from the cerebral hemispheres through the cerebral veins, particularly in its distal one third. The lateral sinuses lie near the mastoid air cells and they are at risk for infectious infiltration and thrombosis. The proximity of the cavernous sinus and the collateralization with the ophthalmic and sphenoparietal veins allows infection to be transmitted easily from the face; this infection is the leading cause of venous thrombosis in the cavernous sinus. There are numerous anatomic variations that may play a role in the interpretation of diagnostic studies. The right lateral sinus frequently dominates the drainage over the left side.* Anatomic variations in the lateral dural sinuses such as this one have implications in making the diagnosis of DST. An isolated lack of filling of the transverse portion of the left lateral sinus is thus more suggestive of congenital hypoplasia than thrombosis. EPIDEMIOLOGY

Although the exact incidence of DST is unknown, it is agreed that this is a relatively rare disease. Most of the estimates are derived from autopsy studies. Ehler and Courville” found 16 cases of superior sagittal sinus thrombosis in a series of 12,500 autopsies. Barnett and Hyland3 found only 39 noninfective DSTs in 20 years that were proved by autopsy. Later autopsy studies reported the incidence to be from a low of 0.039’0’~to a high of 9% in 182 adult cases.24 DST affects all age groups and sexes, with a strong preponderance of women between the ages of 20 and 40.8 This higher incidence may reflect the fact that women in that age group are more likely to use oral contraceptives, be pregnant, and undergo puerperium. PATHOPHYSIOLOGY

Virchow’s triad states that thrombosis is caused by endothelial injury, hypercoagulable state, and stasis of blood. The thrombus acutely formed in the venous system is a red t h r o m b ~ sIt . ~may progressively organize to form fibrous tissues, sometimes showing recanalization. Vascular injury caused by trauma causes local endothelial damage and altered hemodynamics. Trauma, neoplasms, and other mass lesions can cause vascular compression and altered hemodynamics, resulting in DST.20The association of dural arteriovenous fistulas and DST has been recognizedP This is thought to be related to the altered hemodynamics induced by the dural arteriovenous fistula. Hypercoagulable states are associated with numerous conditions



contributing to DST. A hypercoagulable state may be present in a patient who has lupus, Behcet's disease, inflammatory bowel diseases (i.e., ulcerative colitis), Wegener 's granulomatosis, and Cogan's syndr~me.'~, 16, 19, 28 Infection is thought to cause DST by alteration of the coagulation cascade. Hypercoagulable states have been described in infections. Infection used to be a major causal factor for DST; however, with contemporary antibiotic therapy, this has become less common, and antibiotics remain the primary therapy for this form of DST. Ameri and Bousser* reported that 8.2% of DST cases are caused by infection. Despite a long list of possible causes for DST, causal factors still remained undetermined in many cases. Some investigators estimated that as high as 40% of cases were idiopathic? In summary, DST may be associated with numerous conditions. Most conditions involve alterations in physical properties of vasculature, chemical properties of blood coagulation, or hemodynamic properties of blood flow. Extensive workup is usually required for an identification of an underlying cause for DST. CLINICAL PRESENTATION

The clinical presentation of DST varies widely. Headache is the most common and often the earliest symptom. Nausea, vomiting, and visual changes are other symptoms experienced by patients. Increased intracranial pressure is thought to be the underlying cause for these symptoms. Focal neurologic deficits are often caused by venous hypertension and cerebral infarction or hemorrhage. The most common focal neurologic finding is hemiparesis. Aphasia, hemianopsia, or hemisensory deficits may also occur. Seizure is another common symptom. The mode of onset is also quite variable. Although acute presentation can mimic a cerebrovascular accident or tumor, subacute presentations are more common. In 70% of the cases, the patient's complaints are present for days to weeks. The symptoms can be fluctuating or progressive in onset. DIAGNOSIS

Because the clinical presentation is widely variable and symptoms are usually nonspecific, the key to making the diagnosis of DST is a high level of suspicion. Diagnostic modalities currently utilized for the confirmation of DST include computed tomography (CT), magnetic resonance (MR) imaging, and cerebral angiography. CT is usually the initial diagnostic test performed on patients who are suspected to have DST or who present with acute mental deterioration.2, Sometimes a dense triangle, also known as the delta sign, may be seen as the thrombus occupies the superior sagittal sinus, or a clot may also be seen in a transverse sinus (Figs. 1 and 2). Unfortu-



Figure 1. Nonenhanced CT scan demonstrating hyperdense signal, signifying clot in right transverse sinus caused by thrombosis (arrowheads).

nately, the false-negative rate for CT diagnosis of DST is high. It has been estimated to be as high as 25Y0.~~ MR imaging has recently been the chosen modality for detecting DST.26,27 With MR angiography, the arterial and venous phases can be examined concomitantly or separately. MR angiography or MR venography is now the best method for detecting DST. MR imaging offers certain advantages: the thrombus can be directly visualized, and the cerebral lesions, such as edema and hemorrhagic infarct, can be detected. Cerebra1 angiography used to be the standard in making the diagnosis of DST. It is only indicated now when MR imaging diagnosis is uncertain or neuroradiologic intervention is desired. The typical finding is nonvisualization of all or part of a sinus during the venous phase of an angiogram (Fig. 3). THERAPY

Therapy for patients who have DST should be directed at treating the underlying causative process, symptoms secondary to elevated intracranial process, symptoms secondary to elevated intracranial pressure, and seizures or focal deficits caused by cerebral edema and infarction. If an underlying cause is found, then it should be treated. If an



Figure 2. Nonenhanced CT scan demonstrating a delta sign: triangular hyperdensity signifying clot in superior sagittal sinus (arrowheads).

Figure 3. Lateral view of venous phase of right internal carotid arteriograrn demonstrating thrombosis of superior sagittal, transverse, and sigmoid sinuses (arrows).



infectious process is identified, then wide-spectrum antibiotics or drainage of purulent collections should be used in the treatment.2, Cerebral perfusion pressure should be kept at an adequate level to prevent secondary insults. Seizures are frequently part of the symptomatology and should be treated with anticonvulsant medications. HEPARIN THERAPY

The natural course of DST is variable, and the guidelines directing the treatment are controversial. Antithrombotic agents, specifically heparin, have been used with good results. Unfortunately, there is scant data on the true efficacy of heparin treatment. Scattered reports on the successful use of heparin in treating DST exist in the literature.6,23 There is only one prospective, randomized, controlled study in the therapy of DST. Einhaupl et all2 published the results of a small series of 20 patients in 1991. The efficacy of systemic heparin was compared with placebo in a double-blinded randomized study. The group of patients who received heparin had better outcome at 3 days, 8 days, and 3 months. Despite the risk for intracerebral hemorrhage, the benefit of using systemic heparin has been examined in these large retrospective studies and in a small prospective study. The current trend is to use heparin. The goal for heparin anticoagulation is to maintain an activated partial thromboplastin time (aPTT) 2 to 2.5 times the normal aPTT. Once the patient's condition has stabilized, then warfarin therapy is initiated. The therapeutic International Normalized Ratio (INR) is kept between 2 and 3. THROMBOLYTICS

Thrombolytic agents, such as streptokinase, urokinase, and tissue plasminogen activator, have been used systemically in small experimental series. Unfortunately, only anecdotal reports are available in the clinical management of thrombolytic agents.', lo, 14, 15, 25 The major risks of the systemic administration of thrombolytic agents include major gastrointestinal hemorrhage or intracranial hemorrhage. It is suggested that local infusion of thrombolytic agents by means of interventional neuroradiologic techniques can minimize the major complications from systemic thrombolysis. ENDOVASCULAR THERAPY FOR DURAL SINUS THROMBOSIS

Recent advances in endovascular techniques allow selective delivery of thrombolytic agents to dural sinuses where thrombosis occurs. The method for local infusion of thrombolytic agents offers advantages, including minimization of system effects of the thrombolytic agents and



improved local clot lysis with higher concentration of thrombolytic agents. Historically, Scott et alZ1reported the first case of local fibrinolytic therapy. A young patient who had DST and a rapidly deteriorating clinical course was treated with midline craniotomy and direct catheterization of the superior sagittal sinus. Higashida et all7proposed a more aggressive modality of therapy for patients who have clinically deteriorating DST. The investigators successfully performed direct puncture of the superior sagittal sinus in a neonate and infusion of urokinase, resulting in clot lysis over 12 hours. This was the first reported attempt at locally infused thrombolytic treatment for DST without any craniotomy. Barnwell et a14 reported direct endovascular thrombolytic therapy in three patients. All three patients had a dural arteriovenous fistula and were treated by a transjugular direct infusion of urokinase. The period of continuous infusion for thrombolysis ranged between 4 and 10 days. In two patients, the clinical signs and symptoms improved with angiographic evidence of clot lysis and dural sinus recanalization. Angiography indicated that one patient had a partial resolution of a clot in the torcular Herophili and the transverse sinus but showed no clinical improvement. These preliminary results were encouraging and suggested that transjugular local infusion of thrombolytic agents can be an effective treatment for symptomatic, thrombosed dural sinuses. Tsai et alZ5reported five cases of successful transfemoral direct thrombolytic treatment. Smith et a P reported seven cases from their experience. Seven patients who had symptomatic DST and who failed a trial of medical treatment were treated with direct infusion of urokinase into the thrombosed sinus. Patients received urokinase doses ranging from 20,000 to 150,000 U/h with a mean infusion time of 163 hours (range 88 to 24 hours). Patency of the affect dural sinus was achieved with antegrade flow in all patients. Six patients either improved neurologically over their prethrombolysis state or were healthy after thrombolysis. The only complications were an infected femoral access site and transient hematuria. Horowitz et all8 added 12 more cases to the literature. They reported that despite the presence of preinfusion infarct in five patients, four of which were hemorrhagic, they incurred no major therapeutic morbidity. Functional sinus patency was achieved in 11 of 12 patients, with their only true failure in an individual who had symptoms of at least 2 months’ duration. Good to excellent clinical outcome was achieved in 10 of 11patients. Barnwell et a15reported an additional six cases of local thrombolytic therapy. Three patients did well and made a complete recovery. Two of these patients had extensive thrombosis and presented with a more severe clinical picture and made full functional recoveries. One patient, who had extensive DST that had been observed but not treated for 3 weeks, had minimal improvement on the posttherapy angiogram and became blind during the course of therapy from optic neuropathy, probably secondary to optic-nerve damage from increased intracranial pressure. Two patients, who had extensive DST, bilateral parietal lobe infarcts, and coma had no improvement and died, both from intractable hypertension and stroke.




Before initiating thrombolytic therapy, a noncontrast CT scan of the head is obtained to assess the presence of an intracerebral hemorrhage. Although the presence of hemorrhage is not an absolute contraindication to thrombolytics, it must be known and its presence taken into consideration, particularly in regard to dosing the thrombolytics. Once the patient is determined to be a candidate for thrombolysis, they are immediately taken to the interventional suite to undergo emergent cerebral angiography to characterize the extent of thrombosis before a treatment regimen is instituted. The initial step is to gain venous access to the occluded sinus. Typically, a large 6 or 7F guide catheter is navigated into the jugular bulb by means of a transfemoral venous approach (Fig. 4). The thrombolytic catheter is then chosen. For DST the infusion microcatheter is chosen on the basis of its maneuverability and its ability to deliver the agent over a large surface area of thrombus. For this reason, an end-hole catheter is not preferred because the lytic agent only contacts the clot at the end of the catheter. Instead, multiported sidehole catheters, such as the Softstream Tracker-18 (Target Therapeutics, Fremont, CA), are navigated into the sinus so that the majority of ports are in contact with the thrombus. The catheter is navigated over a microguidewire that has good torqueability and stiffness to allow the guidewire to be passed into the occluded segments of the sinus. The critical thing is to deliver the urokinase to as much of the thrombosed sinus as possible. As the

Figure 4. Lateral skull radiograph showing endovascular catheter located in superior sagittal sinus (arrowheads). It is advanced by a femoral venous percutaneous approach through jugular vein, sigmoid and transverse sinuses, and torcula into anterior to middlethird of superior sagittal sinus.



Figure 5. Lateral view of venous phase of right internal carotid arteriogram demonstrating recanalizationof dural sinus after local thrombolytic therapy.

thrombolysis proceeds, the catheter may need repositioning, or a different catheter may be required for accessing other areas of the sinus. Once the microcatheter has been positioned, a dural sinus venogram is obtained to demonstrate the extent and location of the thrombus. The urokinase infusion is then started. The urokinase regiment utilized is based on our experience in comparison with the limited amount of published data. Local administration of low-dose urokinase generally avoids systemic, hemorrhagic effects caused by high-dose intravenous delivery, although the appropriate dose has not yet been well defined. It has been suggested that infusion rates of less than 100,000 U/h are associated with low risk of hemorrhage from systemic fibrinolysis, and that has also been our experience. Infusion of less than 100,000 U of urokinase in the dural sinus of an adult probably will not cause an increase in brain or peripheral bleeding, even if bleeding were present. Once the venogram demonstrates good patency of the sinus, a cerebral arteriogram is performed to evaluate the venous drainage from the brain and the rate of runoff through the previously occluded sinus. The microcatheter is then removed, and the patient is maintained on heparin (Fig. 5). CONCLUSIONS

DST is a relatively rare entity. Its clinical presentation and outcome have a wide spectrum. A high level of suspicion is necessary for clinicians to make the accurate diagnosis. Recent advances in diagnostic and



therapeutic modalities have changed the detection and the prognosis of this entity. MR imaging and MRV have been utilized as standards in diagnostic modalities. Although nonconclusive, antithrombotic agents have been used with success to treat this condition. More recently, interventional neuroradiologic techniques have been utilized for local delivery of thrombolytic agents with initial success. Endovascular techniques offer local delivery of thrombolytic agents; hence superior clot lysis is achieved in the venous sinuses selectively and systemic morbidity from hemorrhagic complications are minimized. The endovascular local thrombolysis techniques will undoubtedly be employed increasingly in the future as the treatment choice for DST. References 1. Alexander LF, Yamamoto Y, et a1 Efficacy of tissue plasminogen activator in the lysis of thrombosis of the cerebral venous sinus. Neurosurgery 26:559-564, 1990 2. Ameri A, Bousser M-G: Cerebral venous thrombosis. Neurol Clin 10(1):87-111, 1992 3. Barnett HJM, Hyland HH: Non-infective intracranial venous thrombosis. Brain 76:36, 1953 4. Barnwell SL, Higashida RT, et al: Direct endovascular thrombolytic therapy for dural sinus thrombosis. Neurosurgery 28:135142, 1991 5. Barnwell SL, Nesbit GM, et al: Local thrombolytic therapy for cerebrovascular disease: Current Oregon Health Sciences University experience (July 1991 through April 1995). J Vasc Interv Radio1 6378S-825, 1995 6. Bousser MG, Chiras J, et al: Cerebral venous thrombosis. A review of 38 cases. Stroke 16~199-213,1985 7. Bousser MG, Russell RR: Cerebral venous thrombosis. London, Academic Press, 1997, pp 385389 8. Canhi C, Barinagarrementeria F Cerebral venous thrombosis associated with pregnancy and puerperium: Review of 67 cases. Stroke 241880-1884, 1993 9. Chiras J, Bousser MG, et al: CT in cerebral thrombophlebitis. Neuroradiology 27145, 1985 10. Di Rocco C, Iannelli A, et a1 Heparin-urokinase treatment in aseptic dural sinus thrombosis. Arch Neurol 38:431, 1981 11. Ehler H, Courville CB: Thrombosis of internal cerebral veins in infancy and childhood. Review of literature and report of five cases. J Pediatr 8:600, 1936 12. Einhaupl KM, Villringer A, et a1 Heparin treatment in sinus venous thrombosis. Lancet 338:597-600, 1991 13. Erez N, Babuna C, et a1 Low incidence of thromboembolic disease. An evaluation of obstetric and gynecologic patients in Istanbul. Obstet Gynecol 27:833, 1966 14. Fletcher AP, Alkjaersig N, et al: A pilot study of urokinase therapy in cerebral infarction. Stroke 7135, 1976 15. Gilbert PC, Welch WC, et al: Isolated deep cerebral venous thrombosis treated by direct endovascular thrombolysis. Surg Neurol48:261-266, 1997 16. Hammans SR, Ginsberg L Superior sagittal sinus thrombosis in Wegener’s granuloma. tosis. J Neurol Neurosurg Psychiatry 52:287, 1989 17. Higashida RT, Helmer E, et al: Direct thrombolytic therapy for superior sagittal sinus thrombosis. ANJR 10:54-S6, 1989 18. Horowitz M, Purdy P, et al: Treatment of dural sinus thrombosis using selective catheterization and urokinase. Ann Neurol 38:58-67, 1995 19. Johns DR Cerebrovascular complications of inflammatory bowel disease. Am J Gastroenterol 86:367, 1991 20. Kuether T, ONeill 0, et al: Endovascular treatment of traumatic dural sinus thrombosis: Case report. Neurosurgery 42:1163-1167, 1998



21. Scott JA, Pascizzi RM, et al: Treatment of dural sinus thrombosis with local urokinase infusion. J Neurosurg 68:284-287, 1988 22. Smith TP, Higashida RT, et a1 Treatment of dural sinus thrombosis by urokinase infusion. AJNR 15:801-807, 1994 23. Standfield FR: Puerperal cerebral thrombophlebitis treated by heparin. BMJ 4:436,1942 24. Towbin A: The syndrome of latent cerebral venous thrombosis. Stroke 4:419, 1973 25. Tsai FY, Higashida RT, et al: Acute thrombosis of the intracranial dural sinus: Direct thrombolytic therapy. AJNR 13:1137-1141, 1992 26. Tsai RY, Wang AM, et al: MR staging of acute dural sinus thrombosis: Correlation with venous pressure measurements and implications for treatment and prognosis. AJNR 16:1021-1029, 1995 27. Tsuruda JS, Shimakawa A, et al: Dural sinus occlusion: Evaluation with phase-sensitive gradient-echo MR imaging. AJNR 12:481488, 1991 28. Wechsler B, Vidailhet M, et al: Cerebral venous thrombosis in Behcet’s disease: Clinical study and long-term followup of 25 cases. Neurology 42614, 1992

Address reprint requests to Frank P. K. Hsu, MD, PhD Oregon Health Sciences University 3181 Southwest Sam Jackson Park Road Mail Code L-472 Portland, OR 97201