Use of thrombolytic therapy in cerebral venous sinus thrombosis with ulcerative colitis.

Cerebral venous thrombosis developing concurrently with active ulcerative colitis poses a therapeutic dilemma. We report the case of a 31-year-old woman who developed dural venous sinus thrombosis during the course of active ulcerative colitis in whom we accomplished clot lysis using intrasinus urokinase. The success of the procedure was assessed by improvement in the patient's neurological condition and resolution of imaging features without any bleeding complications. We also reviewed literature on various modalities of treatment of sinus venous thrombosis in patients with ulcerative colitis and outcome.

Introduction

Ulcerative colitis (UC) is often complicated by various extra-intestinal manifestations during its clinical course. Of these manifestations, thromboembolic complications are well recognized, and their incidence has been reported as varying from 1.2% to 7.5%.[12] Use of anticoagulants or thrombolytic agents against thrombosis associated with UC is controversial due to risk of hemorrhage from gastrointestinal tract. We report a young patient with ulcerative colitis who suffered an hemorrhagic infarction of brain due to venous sinus thrombosis who was successfully treated with local intrasinus urokinase with excellent outcome. We also reviewed the literature about various treatment modalities used in reported cases, which would help in guiding management of similar cases in future.

Case Report

A 31-year-old woman, known patient of UC on steroids for the past one year, presented with headache for one day. Next day she developed sudden onset of weakness of right upper limb and lower limb, associated with progressive inability to speak and comprehend. She did not have vomiting, seizures or loss of consciousness. She also complained of irregular bloody diarrhea and was on amino salycilic acid. There was no history of rash, joint pains or jaundice. She had unexplained first trimester abortions twice. On examination, she had pallor without significant lymphadenopathy. She was conscious and had global aphasia. She had right hemianopia, bilateral papilledema, right upper motor neuron facial nerve palsy and right hemiplegia with power of 1/5 in right upper limb and 2/5 in right lower limb. CT and MRI brain showed hemorrhagic infarct in left parietal region [Figures 1 a and b]. MR venogram revealed thrombosis involving superior sagittal sinus and right transverse sinus, later confirmed by digital subtraction angiography [Figure 2a]. Other laboratory investigations revealed microcytic hypochromic anemia with hemoglobin of 8.5 g/dl. HIV, antinuclear antibody and anticardiolipin antibody was negative. Prothrombotic work up (APLA, Lupus anticoagulant, Protein C, Protein S, Antithrombin 3, ANA, homocysteine) was negative. Colonoscopy revealed multiple hemorrhage prone erosions involving the sigmoid colon. Initially she was started on Low molecular weight heparin for 24 h. As her clinical status continued to worsen, she was taken up for intra sagittal sinus thrombolysis. A catheter was advanced through the right femoral vein to the occluded sagittal sinus. After confirmation of catheter tip, intra sagittal sinus urokinase was given initially as a bolus of 100,000 units which was followed up with continuous urokinase infusion at the rate of 70,000 units per hour by keeping catheter in situ. Check venogram was done at 12, 24, and 48 h. Venogram at 48 h showed partial opening up of superior sagittal sinus and complete opening of right transverse sinus [Figure 2b]. Subsequently infusion was stopped and she was started on low molecular weight heparin later changed to warfarin. Throughout her hospital stay prothrombin and activated partial thrombin time were monitored. During hospital stay she also developed right focal seizures which were controlled with Phenytoin. She was started on full dose Prednisolone and Amino salicylic acid for UC. She showed a rapid neurological improvement in power (upper and lower limb was 4/5) within 3 days and began to speak words with improving comprehension in 1 week. She did not have any bleeding complications. In follow-up 2 months later, she recovered to the point of no residual symptoms.

Figure 1

(a) CT and (b) T2 weighted MRI images showing hemorrhagic infarction of left parietal lobe

Figure 2

(a) Lateral view of the digital subtraction venogram showing poor ante grade flow and substantial superficial collateral drainage indicate thrombosis in the superior sagittal sinus. (b) Repeat digital subtraction venogram, after the infusion of 100,000 U of urokinase through the micro catheter, demonstrating partial recanalization of the superior sagittal sinus

Discussion

There is no consensus in the literature regarding the treatment for the thromboembolic complications in UC. Many reports have followed conservative management as anticoagulant therapy was considered potentially dangerous, because of risk of mucosal bleeding from the UC lesion.[3] We reviewed various treatment modalities used in treatment of ulcerative colitis with CSVT using medline search, findings of which are summarized in Tables 1 and 2[3-18] . Out of 19 cases reported (including our case), 12 patients received no active therapy and there were 3 deaths. Five of them had residual defects as shown in Table 2. Seven patients received heparin and there was one death. Out of seven, three patients were taken up for thrombolytic therapy in view of progressive clinical deterioration on heparin. Low molecular heparin was tried in three cases. Though two patients improved, one died in this group. So far thrombolytic therapy has been tried only in eight cases of CVST (including our case) with underlying ulcerative colitis. Five of them had no residual neurological deficit in follow up and no deaths were reported in this group.[1315] No bleeding complication [intracerebral/other sites]were noted. This is thought to be due to the relatively rapid metabolism of the thrombolytic agent and, thus, the relatively low arterial concentration of the fibrinolytic agent. In our patient also, there was no increase in cerebral or mucosal bleeding after the thrombolytic therapy. Unlike heparin anticoagulation therapy, thrombolytic agents can promptly accomplish two therapeutic goals: (1) attenuation of thrombus progression; and (2) restoration of venous flow. Furthermore, because of the flexible catheters and the rapid systemic inactivation of urokinase, the systemic and intracranial complications appear to be no more than those of systemic anticoagulation in the acute period.

Table 1

Clinical, imaging features, mode of treatment and outcome in patients with ulcerative colitis and sinus venous thrombosis

Table 2

Comparison of outcome in various treatment groups in Ulcerative colitis with sinus thrombosis

The outcome in patients with ulcerative colitis has been poor in the past; 50%--80% of these patients had neurologic sequelae with significant mortality.[2] Given high morbidity and mortality associated and insignificant risk of bleeding complications, early recognition of thrombotic complications and management of patients who have severe neurologic deficit due to CVST with thrombolysis is important for optimal outcome even in presence of active colitis.

Conclusion

The presence of neurologic signs or symptoms or the identification of a parenchymal hematoma in a patient with known ulcerative colitis should prompt a careful search for underlying cortical venous or dural sinus thrombosis. We suggest that patients be managed on individual basis and that thrombolysis could be considered for those patients who have severe neurologic deficit at admission or who continue to deteriorate despite optimal heparin therapy given severe mortality and morbidity associated with disease. This mode of management may be used even in the presence of ulcerative colitis with close monitoring for bleeding complication.