Direct Thrombolysis of Superior Sagittal Sinus Thrombosis withCoexisting Intracranial Hemorrhage

Jesse R. Rael, William W. Orrison, Jr, Nevan Baldwin, and James Sell

Summary: We present a case of dural cerebral venous thrombo-sis with coexisting left frontal hemorrhage that was successfullytreated with 13.79 million units of urokinase over a period of 165hours.

Index terms: Dural sinuses; Thrombosis, dural sinus; Thrombol-ysis

Since the description of cerebral venousthrombosis by Ribe in 1824, numerous articleshave been published detailing the wide spec-trum of clinical presentations, radiographicfindings, and therapeutic options associatedwith this disorder (1). Recent articles haveshown that direct thrombolysis of dural venoussinus thrombosis should be considered for theacutely deteriorating patient who has not re-sponded to conventional medical therapy (2–6). It may be necessary to consider thrombo-lytic therapy in the setting of parenchymalhemorrhage associated with venous infarction.Intracranial hemorrhage may not be an absolutecontraindication for local urokinase therapy inthe symptomatic patient with dural venous si-nus thrombosis; a few cases have been reportedin which thrombolysis was performed for throm-bosis of the superior sagittal sinus in conjunc-tion with cerebral hemorrhage (5, 6). In thisreport, we describe a severely symptomatic pa-tient with dural venous sinus thrombosis andintracranial hemorrhage who was successfullytreated with direct urokinase infusion.

Case ReportA 20-year-old woman had a 1-day history of headache,

confusion, seizure, and progressive deterioration of mentalstatus. She was transferred to our institution after a cranialcomputed tomographic (CT) scan showed a left-sidedfrontal hemorrhage. The patient’s medical history was sig-

nificant for asthma, bronchitis, and oral contraceptive use.On physical examination, there was symmetric withdrawalto noxious stimuli, no verbal response, and no eye opening(Glascow coma score 6).

Endotracheal intubation was performed and a repeatCT study revealed no change in the left frontal lobe hem-orrhage (Fig 1A). Results of baseline coagulation studiesand a hypercoagulable panel were normal. The pathogen-esis of the dural venous thrombosis was thought to beassociated with the use of birth control pills. Because of thepatient’s initially stable condition and known intracranialhemorrhage, treatment began with anticoagulation andmannitol instead of direct intradural thrombolysis. Intrave-nous heparin was started with a loading dose of 5000 Uand a maintenance dose of 1000 U/h. Six hours later, thepatient deteriorated acutely, exhibiting decerebrate pos-turing with fixed and dilated pupils bilaterally. A repeatcranial CT scan showed obliteration of sulci and basilarcisterns, compatible with diffuse cerebral edema (Fig 1B).A magnetic resonance (MR) study confirmed abnormallyincreased T1-weighted signal in the superior sagittal sinus,compatible with methemoglobin (Fig 1C). (MR angiogra-phy was not available at our institution at the time of thispatient’s admission.) An emergency angiogram revealedocclusion of the superior sagittal sinus, faint opacificationof the transverse sinuses, and propagation of thrombus tocortical veins (Fig 1D and E). The 5F vascular sheath usedfor the first cerebral angiogram was removed prior to he-parinization but in retrospect would have been of benefit ifleft in place. Great care was taken during the repuncturingof the femoral vessels while the patient was on heparin.Because of the life-threatening deterioration of clinical sta-tus and the propagation of thrombus, a decision was madeto proceed with thrombolysis.

Using a right transfemoral vein approach, we gentlytransgressed the thrombosed right internal jugular veinand the sigmoid, right transverse, and superior sagittalsinuses to the level of the torcular Herophili using a twist-able hydrophilic guidewire and angled 45° catheter.

The twistable wire was removed and a side-hole infu-sion wire was introduced via the guiding catheter to the

Received September 27, 1995; accepted after revision October 9, 1996.From the Departments of Radiology (J.R.R., W.W.O., J.S.), Neurology (J.R.R., W.W.O.), and Surgery (N.B.), the University of New Mexico School of

Medicine, Albuquerque.Address reprint requests to Jesse R. Rael, MD, Department of Radiology, the University of New Mexico, Albuquerque, NM 87131.

AJNR 18:1238–1242, Aug 1997 0195-6108/97/1807–1238 © American Society of Neuroradiology

1238

anterior aspect of the superior sagittal sinus. A sinusvenogram confirmed the presence of extensive thrombusinvolving the entire superior sagittal sinus to the torcularHerophili (Fig 1F). Thrombolysis of the superior sagittalsinus was initially performed with 250 000 U of urokinasein a pulse-spray manner though the side-hole infusion wireover a period of 2 hours. A sinus venogram after urokinaseinfusion revealed improvement in cortical vein flow butpersistent thrombus within the sinus.

Urokinase was administered by means of a constantinfusion method at a rate of 80 000 U/h (20 000 U/h viaangled guiding catheter; 60 000 U/h via side-hole infusionwire). Fibrinogen levels were monitored every 4 to 6 hoursduring the course of the urokinase infusion. A continuousheparin infusion was used to maintain the partial throm-boplastin time at twice that of the control value.

The side-hole infusion wire was repositioned so as tolyse the entire superior sagittal sinus thrombus. A cranialCT scan revealed improved visibility of the basilar cisternswith no change in the frontal lobe hemorrhage.

Daily dural venography performed via the infusion wireand in the venous phase via carotid artery injections re-vealed progressive lysis of the dural vein thrombus. Theoverall infusion time was 165 hours, with a total urokinasedose of 13.79 million units. Repeat venography revealedprogressive lysis of the dural sinuses with improved bloodflow. Daily cranial CT scans revealed no change in the leftfrontal lobe hemorrhage.

At 1 week, venography revealed near total lysis of su-perior sagittal and transverse sinus thrombus (Fig 1G andH). The infusion wire and 45° and guiding catheters wereremoved. A cranial CT obtained on the last day of infusionshowed evolution of the left frontal hemorrhage withoutnew hemorrhage (Fig 1I). The first signs of consciousnessoccurred at day 4 of thrombolysis. At this time, the patientwas somnolent but arousable. She recognized family andwould nod appropriately to simple questions. At the timeof catheter and wire removal, she was awake and orientedwith no focal sensory or motor abnormalities. Extubationwas difficult because of the patient’s asthma and bronchi-tis, but was accomplished 17 days after admission. Anti-coagulation therapy was converted from heparin to warfa-rin. She was discharged after a 30-day hospital stay withno focal neurologic deficit, although neuropsychiatric test-ing revealed a mild impairment in the area of numericalprocessing. Warfarin was maintained for 6 months. A sub-sequent follow-up MR venogram showed flow signalthroughout the superior sagittal sinus. Altered signal in theposterior superior sagittal sinus was thought to be turbu-lent flow artifact (Fig 1J).

Discussion

Acute occlusion of the superior sagittal sinus,particularly the posterior half, and the dominanttransverse and sigmoid sinuses can lead to sig-nificant cerebral edema, increased intracranial

AJNR: 18, August 1997

pressure, hydrocephalus, and venous conges-tion with resulting hemorrhage and/or infarction(4, 7). Recanalization of the affected vessels isessential for patients with severe symptoms,particularly if collateral vessels are absent orthrombosed. Presently, direct thrombolytictherapy should be considered for patients inwhom medical therapy fails or in those whodeteriorate clinically (2, 3, 6). Experience withthrombolysis in the setting of sinus thrombosiswith coexisting cerebral hemorrhage is limited(3, 6). Initially, thrombolytic therapy was con-sidered in our case after the first angiogram.However, because of the patient’s initial clinicalstability, we decided that treatment with heparinwas most appropriate. When the patient showedfurther clinical deterioration, with CT findings ofincreased cerebral edema and impending her-niation, the decision to proceed with thrombo-lytic therapy was considered imperative.

Much of what we know about thrombolysiscomes from others’ experience with thrombol-ysis of arterial and bypass graft occlusions (8–10). It has been shown that optimal thromboly-sis is best achieved when urokinase is infuseddirectly into the thrombus, as opposed to pe-ripheral intravenous administration (11). Otherinvestigators have reported shortened time tothrombolysis by using a pulse-spray techniquethrough side-hole catheters, because intra-thrombic injection of urokinase macerates theclot and augments the amount of its interactivearea (6, 9, 11). It was postulated in our case thatlocalized thrombolysis of the superior sagittalsinus with urokinase would minimize perfusionof infarcted or damaged brain tissue and lessenthe risk of additional brain hemorrhage. Regard-ing the risk of a systemic fibrinolytic state, it wasfurther postulated that direct thrombolytic ther-apy would minimize the risk of a systemic fi-brinolytic state because of the limited circula-tion and short half-life of urokinase (11 to 16minutes) (12). Data from studies in whichrecombinant tissue plasminogen activatorwas given for acute ischemic stroke have shownno systemic hemorrhagic complications (13,14).

The use, optimal technique, and dosage forintrathrombic infusion of urokinase in thethrombosed dural sinus have not been well de-fined, particularly in those patients with preex-isting parenchymal hemorrhage. Horowitz andcolleagues (6) reported 13 patients with duralsinus thrombosis treated with selective cathe-

THROMBOSIS 1239

1240 RAEL AJNR: 18, August 1997

terization and urokinase therapy. In their series,11 of 12 patients had good outcomes, includingfour patients with hemorrhagic infarcts. Hi-gashida and coauthors (5) described directthrombolysis in a newborn child with superiorsagittal sinus thrombosis and coexisting paren-chymal hemorrhage. Unfortunately, the throm-bolytic dose may be difficult to correlate withhemorrhage (3, 11, 13, 14). Administereddoses of urokinase should therefore be kept aslow as possible to minimize the risk of hemor-rhage. Reported urokinase doses and infusiontimes vary among authors, ranging from250 000 U to 500 000 U (3, 7) for the initialbolus; however, 250 000 U administered over 1hour seems to be the most common. Long-termdural sinus infusion doses of 80 000 to 200 000U have been reported without significant fibri-nolysis (2, 3, 6). In the present case, an initialdose of 250 000 U of urokinase was adminis-tered over 2 hours using a pulsed-spray tech-nique. Urokinase was then infused at a rate of80 000 U/h for a total infusion time of 165

hours. Daily cranial CT scans revealed no prop-agation of the preexisting parenchymal hemor-rhage or areas of new hemorrhage. The absenceof rehemorrhage was verified by an indepen-dent review of CT scans performed by a neuro-radiologist who was blinded to the details of thecase. Daily fibrinogen levels were normal; how-ever, normal fibrinogen levels do not ensureagainst a fibrinolytic state. The correlation ofabnormal plasma fibrinogen levels with the riskof hemorrhage appears to be weak at best (11).The absence of additional hemorrhage probablyhad nothing to do with monitoring fibrinogenlevels but rather with the negligible risk of localthrombolytic therapy. In our case, we probablywould have discontinued the urokinase if levelshad dropped below 100 mg/dL, a level that hasbeen reported as necessary for systemic hemo-stasis (12).

A case of parenchymal brain hemorrhage as-sociated with thrombolysis of the dural sinushas been reported (15). In that case, both theurokinase and heparin were subsequently dis-

Fig 1. A 20-year-old woman with headache, confusion, seizure,and deteriorating mental status.

A, Unenhanced axial CT scan shows left-sided frontal lobe hem-orrhage and surrounding edema.

B, Unenhanced axial CT scan 1 day after admission shows ef-facement of sulci and basilar cisterns, compatible with diffuse ce-rebral edema. The left frontal hemorrhage is unchanged.

C, T1-weighted MR image shows increased signal in the superiorsagittal sinus, indicative of thrombus.

Anteroposterior (D) and lateral (E) views of right internal carotidangiography, late venous phase, show occlusion of the superiorsagittal sinus with minimal opacification of the transverse sinusesand involvement of cortical veins on day 1 of thrombolysis.

F, Lateral superior sagittal sinus venogram obtained through theinfusion wire reveals extensive thrombus within the superior sagittalsinus.

Anteroposterior (G) and lateral (H) views of right internal carotid angiography, venous phase, on last day of thrombolysis show neartotal lysis of the thrombus within the superior sagittal and transverse sinuses.

I, Unenhanced CT scan on last day of urokinase infusion shows evolution of left frontal hemorrhage and better delineation ofsurrounding edema. Increased attenuation seen in the anterior mid-falx region is thought to be bone artifact and perhaps mild residualthrombus in the anterior superior sinus.

J, MR venogram of the superior sagittal sinus shows flow signal throughout the sinus.

AJNR: 18, August 1997 THROMBOSIS 1241

continued. Systemic anticoagulation was rein-stated 48 hours after resolution of hemorrhage,and the patient subsequently did well.

Ideally, one would like to continue thrombol-ysis until the dural sinus shows a normal ap-pearance and flow. However, since prolongedinfusion increases the risk of thrombolytic-re-lated complications, particularly catheter-re-lated infection, it may sometimes be necessaryto settle for a less than optimal result. The timeof dural sinus thrombolysis varies from 88 to244 hours, with an average time of 171 hours(3). In our case, the infusion was discontinuedafter 165 hours with a less than perfect-appear-ing superior sagittal sinus. The sinus venogramrevealed brisk flow through the superior andtransverse sinuses with areas of residual throm-bus, which was not flow limiting. Our decision toterminate was also influenced by the patient’snearly normal mental status as well as fever,

which was presumed to be related to pulmonaryatelectasis/infiltrate. Dural sinus venous pres-sures may provide an objective means of decid-ing when to discontinue thrombolytic therapy. Avenous pressure of less than 17 mm Hg hasbeen associated with an absence of parenchy-mal injury and clinically significant symptomsand may be an indication to terminate the infu-sion (7).

The use of heparin for cerebral venous throm-bosis has been the subject of considerable de-bate. Proponents of anticoagulation believe thatheparin will prevent further propagation ofthrombus and allow formation of collaterals.Others believe that heparin may promote intra-cranial hemorrhage (1, 16). At present, it isbelieved that heparin is not only safe but bene-ficial in the treatment of symptomatic patientswith cerebral venous thrombosis, even in thesetting of intracerebral hemorrhage (5, 6).

Regarding postthrombolytic care, Bousser etal (1) initially used heparin for 1 to 3 monthsand then oral anticoagulants for another 4 to 8months. We started Warfarin once the patientshowed clinical improvement and significant ly-sis of the cerebral thrombus. Warfarin was thencontinued for 6 months and daily aspirin rec-ommended indefinitely. Patients can then befollowed up with serial MR imaging and/or MRangiography.

In conclusion, thrombosis of the dural sinusescan be life threatening as a consequence ofpoor cerebral venous outflow. In cases such asours, restoration of venous outflow may be cru-cial for preventing such complications as in-creased intracranial pressure, edema, infarc-tion, and brain herniation. While our results withthis patient were dramatic, it is possible that thiscase represents an exception and that intraduralsinus thrombolysis could potentiate additionalintracranial hemorrhage and increased mortal-ity. We expect that the criteria for treatment ofsymptomatic cerebral venous thrombosis willbecome better defined with additional experi-ence and future research.

References1. Bousser MG, Chiras J, Bories J, Castaigne P. Cerebral venous

thrombosis: a review of 38 cases. Stroke 1985;16:199–2122. Barnwell SL, Higashida RT, Halbach VV, Dowd CF, Hieshima GB.

Direct endovascular thrombolytic therapy for dural sinus throm-bosis. Neurosurgery 1991;28:135–142

3. Smith TP, Higashida RT, Barnwell SL, et al. Treatment of dural

1242 RAEL

sinus thrombosis by urokinase infusion. AJNR Am J Neuroradiol1994;15:801–807

4. Tsai FY, Higashida RT, Matovich V, Alfieri K. Acute thrombosis ofthe intracranial dural sinus: direct thrombolytic treatment. AJNRAm J Neuroradiol 1992;13:1137–1141

5. Higashida RT, Helmer E, Halbach VV, Hieshima GB. Direct throm-bolytic therapy for superior sagittal sinus thrombosis. AJNR Am JNeuroradiol 1989;10(Suppl):S4–S6

6. Horowitz M, Purdy P, Unwin H, Carstens G, et al. Treatment ofdural sinus thrombosis using selective catheterization and uroki-nase. Ann Neurol 1995;38:58–67

7. Tsai FY, Wang A, Matovich VB, et al. MR staging of acute duralsinus thrombosis: correlation with venous pressure measurementsand implications for treatment and prognosis. AJNR Am J Neuro-radiol 1995;16:1021–1029

8. Bookstein JJ, Valji K. Pulse-spray pharmacomechanical throm-bolysis: updated clinical and laboratory observations. Semin In-terv Radiol 1992;9:174–181

9. Bookstein JJ, Fellmeth B, Roberts A. Pulsed-spray pharmacome-chanical thrombolysis: preliminary clinical results. AJR Am JRoentgenol 1989;152:1097–1100

10. Valji K, Roberts AC, Davis GB, Bookstein JJ. Pulsed-spray throm-bolysis arterial and bypass graft occlusions. AJR Am J Roentge-nol 1991;156:617–621

11. Marder VJ, Sherry S. Thrombolytic therapy: current status. N EnglJ Med 1988;318:1585–1595

12. Castaneda-Zuniga WR, Tadavarthy SM. Interventional Radiology.2nd ed. Baltimore, Md: Williams & Wilkins; 1992:603

13. Marler JR, The National Institute of Neurological Disorders andStroke rt-PA Stroke Study Group. Tissue plasminogen activatorfor acute ischemic stroke. N Engl J Med 1995;333:1581–1587

14. Hacke W, Markku K, Cesare F, et al. Intravenous thrombolysiswith recombinant tissue plasminogen activator for acute hemi-spheric stroke. JAMA 1995;247:1017–1025

15. Eskridge JM, Wessbecher FW. Thrombolysis for superior sagittalsinus thrombosis. J Vasc Interv Radiol 1991;2:89–94

16. Estanol B, Rodriguez A, Conte G, Aleman JM, Loyo M, PizzutoJ. Intracranial venous thrombosis in young women. Stroke 1979;10:680–684

AJNR: 18, August 1997