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A 27-year-old man presents to the emergency department after suddenly experiencing significant weakness and loss of sensation on his right side. Before these symptoms developed, he had been troubled by a persistent headache and several generalized seizures. He reports no prior history of cerebrovascular accident (CVA) or transient ischemic attack (TIA).

The patient explains that he has had ulcerative colitis (UC) for several years, which was previously treated with 5-aminosalicylic acid (mesalamine), and 6-mercaptopurine. However, he had a relapse recently, and had to be hospitalized for treatment and received a 10-day course of steroid therapy. He notes that following his return home from the hospital, his bowel movements continued to be bloody.

Physical examination finds reduced strength (2/5), diminished sensation, and brisk reflexes affecting his right side.

Imaging work-up of the head and brain with a computed tomography (CT) scan and magnetic resonance imaging (MRI) reveals a left paramedian frontoparietal cortical infarct secondary to cerebral venous sinus thrombosis.

Laboratory Investigations

Results of tests of serum lipids, and liver and renal function tests are unremarkable. The patient's glycated hemoglobin (HbA1c) is 6.5%. Coagulopathy workup, including tests for factor V Leiden mutation, complement factors, and proteins C and S levels, also have normal findings except for a slightly increased international normalized ratio of 1.2.

Flexible sigmoidoscopy reveals diffuse shallow ulcerations suggesting severe UC with a Mayo score or Disease Activity Index of 11.

Imaging Shows a Clue

Subsequent magnetic resonance venogram (MRV) of the head identifies thrombosis of the left posterior frontal and anterior parietal cerebral cortex veins near the vertex, which has interrupted venous flow. Doppler ultrasound shows no sign of deep vein thrombosis affecting the legs.

The patient undergoes a transthoracic contrast-enhanced echocardiogram, and is found to have a normal ejection fraction with no evidence of intracardiac thrombus or patency of the foramen ovale.

Diagnosis and Treatment

Clinicians determine that the patient has left cerebral venous sinus thrombosis (CVT) complicated by left frontotemporal infarction.

He has been receiving steroid therapy, 5-aminosalicylic acid, and infliximab. The treatment team initiates anticoagulation therapy with heparin infusion to address his cerebral venous sinus thrombosis. The patient also receives the anti-epileptic levetiracetam to manage his seizures.

As his condition gradually improves, he reports fewer bloody bowel movements. Upon transfer to a rehabilitation facility, he receives treatment with the anticoagulant apixaban. He is referred for multi-disciplinary management with follow-up at a gastroenterology and neurology outpatient clinic.

CVT symptom onset may be acute or gradual, according to the multinational, observational International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) study. That showed that among 624 patients, acute symptom onset (<48 hours) was evident in 37% of patients, subacute (48 hours to 30 days) in 56% of patients, and chronic (>30 days) in 7% of patients.

Discussion

As this ¹ demonstrates, patients with inflammatory bowel disease (IBD) are at risk of thromboembolic events,^2,3 theoretically related to the effects of a chronic inflammatory state on coagulation. Aseptic cerebral venous sinus thrombosis is one rare complication of IBD⁴ and can have serious consequences if not diagnosed and treated promptly.

Patients with IBD have about three times the risk of developing venous thromboembolism – most commonly deep vein thrombosis (DVT) and pulmonary embolism (PE)⁴ – when compared with the general population, even after abnormalities of pro-thrombotic factors have been corrected.⁵

The authors reporting this case explained that hypercoagulable states, including hyperhomocysteinemia and mutation of factor V Leiden, have been noted in patients with IBD. Cerebral venous sinus thrombosis is a well-documented cause of acute onset neurological dysfunction in patients with IBD,⁶ the authors added.

They said that as reflected in this case, younger and male patients with IBD are at greater risk, in contrast to cerebral venous thrombosis due to other causes, and the sagittal and lateral venous sinuses are more likely to be affected.⁷

The large of adults with venous sinus thrombosis found that 1.6% had IBD. Risks were also increased in women during pregnancy and postpartum periods, and in the presence of oral contraceptive use, smoking, malignancy, dehydration, substance abuse, infection, and head trauma; almost half of the patients had multiple risk factors.⁸

The clinicians reporting this case noted that although presenting symptoms can vary, they typically involve new-onset headaches. Symptoms such as weakness and loss of function affecting one limb or one side of the body have also been noted, along with confusion, changes in mental status, and signs suggestive of increased intracranial pressure.⁹

The authors said that IBD patients presenting with these new-onset symptoms, particularly at the time of flare of their IBD, should be screened and evaluated for prothrombotic conditions as part of the initial clinical workup,¹⁰ as by the American Heart Association/American Stroke Association.

Confirming the Diagnosis

Diagnosis of cerebral venous sinus thrombosis may be confirmed with imaging studies. For example, head CT without contrast can reveal associated hemorrhagic infarction, thus avoiding inappropriate anticoagulation treatment. Up to 30% of these patients will have intracerebral hemorrhage, predictive of poor clinical outcomes.^10,11

The gold standard for diagnosis is MRI with and without contrast and MRV since they allow for direct visualization of the thrombus.¹⁰ CT venography allows for rapid and reliable confirmation of diagnosis.¹²

Treatment

Once diagnosis has been confirmed, recommended treatment is short-term anticoagulation therapy for 3-6 months in patients without contraindications. Thrombolytic therapy in patients has not been studied sufficiently to be recommended.¹³ Because recurrence of thromboembolic events is uncommon, long-term therapy is not indicated for most patients, the authors said.¹⁴

Conclusion

The case report authors concluded that thromboembolic events are a well-documented extraintestinal manifestation of IBD, and that this case joins other ¹⁵ highlighting the critical need for early recognition of clinical signs and neurological symptoms in patients with IBD during disease flares; this allows for timely anticoagulation therapy and improved neurological outcomes.

References

1. AO Abdalla, et al: A Case of Cerebral Venous Sinus Thrombosis Presenting During Relapse of Ulcerative Colitis. Am J Case Rep 2019; 20: 419-422

2. DeFilippis EM, et al: Cerebral venous thrombosis in inflammatory bowel disease. J Dig Dis 2015; 16(2): 104–108

3. Algahtani FH, et al: Thromboembolic events in patients with inflammatory bowel disease. Saudi J Gastroenterol 2016; 22(6): 423-427

4. Talbot RW, et al: Vascular complications of inflammatory bowel disease. Mayo Clin Proc 1986; 61(2): 140-145

5. Tan VP, et al: Venous and arterial disease in inflammatory bowel disease. J Gastroenterol Hepatol 2013; 28(7): 1095-1113

6. Meher LK, et al: Unusual case of cerebral venous sinus thrombosis in patients with ulcerative colitis in remission. J Clin Diagn Res, 2016; 10(5): 35–36

7. Giannotta M, et al: Thrombosis in inflammatory bowel diseases: What's the link? Thromb J 2015; 13: 14

8. Ferro JM, et al, ISCVT Investigators: Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural

Sinus Thrombosis (ISCVT). Stroke. 2004;35:664–670

9. Ferro JM, et al: Cerebral vein and dural sinus thrombosis in Portugal: 1980–1998. Cerebrovascular Diseases 2001; 11(3) :177–182

10. Saposnik G, et al: Diagnosis and management of cerebral venous thrombosis: A statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2011; 42(4): 1158-1192

11. Bousser MG, Ferro JM: Cerebral venous thrombosis: An update. Lancet Neurol 2007; 6(2): 162-170

12. Linn J, et al: Diagnostic value of multidetector-row CT angiography in the evaluation of thrombosis of the cerebral venous sinuses. Am J Neuroradiol 2007; 28(5): 946-952

13. Canhao P, et al: Thrombolytics for cerebral sinus thrombosis: A systematic review. Cerebrovasc Dis 2003; 15(3): 159-166

14. Preter M, et al: Long-term prognosis in cerebral venous thrombosis. Follow-up of 77 patients. Stroke 1996; 27(2): 243–246

15. Conners LM, et al: Cerebral Venous Sinus Thrombosis in a Patient with Ulcerative Colitis Flare. Case Rep Neurol Med; 2018: 5798983

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