Isolated cortical venous thrombosis after fetal demise

Abstract

Isolated cortical venous thrombosis (ICVT) occurring in the absence of dural venous thrombosis, constitutes about 2%–5% of all cerebral venous thrombosis. Its vague, non-specific presentation makes it a difficult and challenging diagnosis that needs an extensive workup especially in young patients. Outcome and prognosis depend mainly on early diagnosis and treatment. Here we discuss the clinical presentation, diagnosis and the treatment of a young woman diagnosed with ICVT with acute ischaemic venous stroke, in the setting of eclampsia and family history of coagulation disease.

Background

Isolated cortical venous thrombosis (ICVT) occuring in the absence of dural venous thrombosis, constitutes about 2%–5% of all cerebral venous thrombosis.^{1 2} Its vague, non-specific presentation makes it a difficult and challenging diagnosis that needs an extensive workup, especially in young patients. Outcome and prognosis depend mainly on early diagnosis and treatment. Here we discuss the clinical presentation, diagnosis and treatment of a young woman diagnosed with ICVT with acute ischaemic venous stroke in the setting of pre-eclampsia and a family history of coagulation disease.

Case presentation

A 36-year-old woman presented to our institute with new onset of sudden right-arm weakness and abnormal shaking movements in her arms that lasted for a few seconds without affecting her level of consciousness (simple partial seizure). One month prior to the presentation, she had severe pre-eclampsia at 22 weeks of her first pregnancy based on persistent elevated blood pressure and severe headache, resulting in fetal demise. Her mother had a history of pulmonary embolism due to activated protein C resistance disease (Leiden) at the age of 44. On physical examination, a decrease in her right-upper limb motor power down to 3 over 5 was noted while the motor power was 5 over 5 in other limbs. Other aspects of neurological examination were intact and no other neurological deficits were noted.

Investigations

The workup started with regular labs and immediate imaging. CT of the head without contrast demonstrated a wedge-shaped infarct in the left frontoparietal convexity and hyperdense extra-axial tubular structure at the vertex adjacent to the left frontoparietal junction within the left vein of trolard, likely indicative of intraluminal thrombus (figure 1). After that, magnetic resonance venography demonstrated hypoplastic left transverse sinus, left sigmoid sinus and straight sinus with suspicion of thrombus in a cortical vein (figure 2A,B). Therefore, an MRI with contrast-T2 of the brain was obtained and demonstrated abnormal, confluent signal throughout the subcortical white matter within the superior posterior left frontal lobe, including the precentral gyrus, as well as the superior aspect of the left postcentral gyrus. Restricted diffusion was present within the superior lateral left frontal lobe cortex, which was interpreted as left frontoparietal vertex cortical venous thrombosis and early subacute venous ischaemia within the superior lateral left frontal lobe (figure 3A–C). Further stroke up, which included carotid ultrasound and echocardiogram were done and did not show any significant pathology. Also 24 hours electroencephalography (EEG) showed left cerebral slowing without any seizure activity. Haematology team was consulted and they recommended thrombophilia workup (levels of protein C, protein S, lupus anticoagulant and antithrombin III) which excluded thrombophilia.

Figure 1.

CT head without contrast: wedge-shaped infarct in the left frontoparietal convexity and hyperdense extra-axial tubular structure at the vertex adjacent to the left frontoparietal junction within the left vein of trolard likely indicative of intraluminal thrombus.

Figure 2.

Magnetic resonance venography: superior sagittal sinus, straight sinus, bilateral transverse and sigmoid sinuses are patent. Left transverse and sigmoid sinus and straight sinus are hypoplastic suspicion of thrombus in a cortical vein (arrows).

Figure 3.

Brain MRI showed abnormal, confluent signal throughout the subcortical white matter within the superior posterior left frontal lobe, including the precentral gyrus, as well as the superior aspect of the left postcentral gyrus.

Outcome and follow-up

The patient was transferred to our stroke unit and started on aspirin, statin, heparin drip and leivrectam. Over the next few days, the weakness of her right arm improved and no further seizures were noted. The heparin drip was switched to enoxaparin and warfarin was started for bridging. After that she was discharged to the acute rehabilitation facility for a few weeks.

Discussion

ICVT usually presents in middle-aged women,³ with significant provoking risk factors like pregnancy, oral contraceptives, androgen use,⁴ infection, thrombophilia, inflammatory bowel disease,^{5 6} Hodgkin disease,⁷ nephrotic syndrome and systemic lupus erythematosus.⁸ According to a recent systematic review, the most common risk factors were oral contraceptive use (21% of women), pregnancy (35% of women), infection (19%)and lumbar puncture (16%).³ Protein C resistance is considered one of the major causes of inherited thrombophilia and has been associated with cerebral venous thrombosis.⁹ Although our patient’s mother had protein C resistance, the workup was negative and protein C resistance was excluded. Other risk factors that were present in our patient were pregnancy, pre-eclampsia and a family history of protein C deficiency.

Clinically, cortical venous thrombosis usually presents with headache and seizures and focal neurological signs include motor and sensory defects, aphasia, hemianopia and dyslexia.^{10 11} According to a recent systemic review, headache is the most common presenting symptom (71%), followed by seizures (58%) and focal neurological signs (26%).³ The patient in our case presented with new onset of weakness and simple partial seizures. However, the presentation was confounded by a recent severe pre-eclampsia and fetal demise 1-month prior to the presentation.

There are different types of diagnostic modalities that can be used to investigate ICVT, including CT and MRI. Head CT may show focal oedema, haemorrhage and cord sign (obstructive lesion in the adjacent venous structures, as first described by Bunanon on 1978).^{2 12} It can also show a tubular hyperdensity in the right central sulcus,^{2 13 14} which indicates an early disease, seen in 20%–25% of cases,¹⁵ and disappears after 2 weeks.¹⁶ However, this sign is not specific and can be seen in other conditions like polycythaemia, and dehydration.² In our case, CT head without contrast showed infarction in the left frontoparietal convexity and intraluminal thrombus in the left vein of trolard.

MRI of the brain can detect the thrombus and the reactive inflammatory changes secondary to venous congestion of the brain parenchyma.¹⁷ In the first week, it will appear as isotense on T1 and hypotense on T2, T2-WI, T2 FLAIR and diffusion images.^17–19 During the second week, it will appear as hyperintense in all MRI sequences;²⁰ that is why it is called hyper-intense vein sign.² In our patient, brain MRI with contrast demonstrated left frontoparietal vertex cortical venous thrombosis and early subacute venous ischaemia within the superior lateral left frontal lobe without definite haemorrhagic transformation, midline shift and superimposed dural venous sinus thrombosis. Even with extensive diagnostic modalities, cortical venous thrombosis is difficult to diagnose because of the size and the location of these veins; so other diagnostic modalities like angiogram can be used which may show indirect signs like tortuous veins, delayed local venous drainage and collateral veins.²¹

The treatment mainly depends on anticoagulation. Multiple studies suggest that anticoagulation, rather than antiplatelets, is better than placebo which is reasonable, given that the pathophysiology of cortical venous thrombosis depends mainly on Virchow’s triad in contrast to arterial stenosis.^22–24 There is no consensus regarding the duration of therapy but for idiopathic ICVT the treatment may extend to 12 months. On the other hand, for secondary ICVT in the setting of provoking risk factors, the duration of treatment can be to 3–6 months.¹³ In case of seizure related to ICVT, antiepileptic medications can be continued for 6–12 months but there is no need for prophylactic antiepileptic medications in absence of seizures.¹¹ Aspirin and statin are considered the cornerstones in the treatment of ischaemic arterial stroke but their role in venous thrombosis is unclear due to lack of clinical trials in the literature.²⁵ In our case, the patient was started on heparin drip followed by enoxaparin as bridge to warfarin, and then she was started on aspirin and statin as part of her stroke treatment. For seizure workup, the EEG was negative for any epileptiform activity but she was started on levetiracetam because she had had a seizure.

Regarding the outcome, most reported cases improved with anticoagulation, aspirin and statin,7 13 14 22 24 26 and that was the case in our patient as her right-upper limb weakness improved within few days of starting treatment.

Learning points.

• Isolated cortical venous thrombosis (ICVT) is a challenging diagnosis and requires extensive work up in young patients.

• There are multiple types of diagnostic modalities that can be used to investigate ICVT including CT and MRI.

• The treatment for iICVT is anticoagulation treatment.