2025 Volume 12 Pages 377-382
Cerebral venous sinus thrombosis (CVST) is rare but serious adverse complication of coronavirus disease 2019 (COVID-19) vaccination. CVST can sometimes lead to development of dural arteriovenous fistula (DAVF), but DAVF secondary to CVST following COVID-19 vaccination is rarely reported. Here, we present a case of CVST occurring after COVID-19 vaccination, followed by subsequent development of DAVF, which was successfully treated. A 45-year-old male presented with headache and progressive visual impairment beginning 4 days after COVID-19 vaccination. Papilledema was noted. Cerebrospinal fluid pressure was elevated at 300 mmH2O, and magnetic resonance imaging (MRI) revealed right transverse sinus thrombosis, prompting initiation of anticoagulant therapy. Four months later, MRI suggested DAVF in right transverse sinus, and he was referred to our department. Digital subtraction angiography confirmed DAVF in right transverse sinus, as well as concurrent convexity DAVF and pial arteriovenous fistula over right vein of Labbé, all draining solely into right vein of Labbé. Anticoagulation therapy was discontinued due to aggressive nature of this DAVF. Transarterial embolization (TAE) with Onyx was performed in 2 sessions, achieving complete occlusion of shunt. Postoperatively, anticoagulation therapy was not resumed. Ten months later, the patient again experienced visual deterioration. Recurrence of convexity DAVF over right vein of Labbé was identified, and TAE with Onyx was performed again, resulting in successful shunt occlusion. Postoperatively, anticoagulant therapy was resumed. The patient's visual acuity gradually improved, and at 18 months post-treatment, no recurrence was observed. CVST following COVID-19 vaccination can progress to DAVF; therefore, careful follow-up is recommended.
Cerebral venous sinus thrombosis (CVST) is a cerebrovascular disease characterized by venous congestion caused by thrombosis within the cerebral venous sinuses, leading to cerebral infarction, hemorrhage, and edematous changes. CVST is one of the rare and serious complications following coronavirus disease 2019 (COVID-19) vaccination.1) CVST after COVID-19 vaccination has been observed more frequently with adenovirus vector vaccines, such as the Oxford-AstraZeneca vaccine (AZD1222 [ChAdOx1]) and Johnson & Johnson COVID-19 vaccine (JNJ-78436735 [Ad26.COV2.S]), with an incidence approximately 10 times higher than that observed with messenger ribonucleic acid (mRNA) vaccines, such as the Moderna vaccine (mRNA-1273) and Pfizer/BioNTech vaccine (BNT162b2).2)
Dural arteriovenous fistula (DAVF) is thought to occur spontaneously, but it can also arise secondary to pathologies such as CVST, head trauma, craniotomy, or venous sinus compression by a tumor. DAVF secondary to CVST is known, but DAVF following CVST induced by COVID-19 vaccination is rare. Here, we report a case of DAVF following CVST after mRNA COVID-19 vaccination, requiring multiple treatments.
A 45-year-old male with no significant medical history received his first dose of the Moderna vaccine (mRNA-1273). Four days later, the patient developed symptoms of headache and bright lines in his visual field. He visited a local ophthalmologist, who identified bilateral papilledema and referred him to the Department of Neurology. Visual acuity testing revealed corrected visual acuity of 0.9/0.8 in the right and left eyes, respectively, and fundoscopic examination showed bilateral papilledema. Lumbar puncture revealed a pressure of 300 mmH2O. Laboratory findings were as follows: white blood cell count 5,150/μL, hemoglobin 15.6 g/dL, platelets 243,000/μL, prothrombin time-international normalized ratio 0.91, activated partial thromboplastin time 30.7 sec, fibrin degradation products <2.5 μg/mL, D-dimer 0.8 μg/mL, antithrombin III 87.1%, total homocysteine 11.8 nmol/mL, protein C antigen 115%, protein S antigen 88%, antinuclear antibody titer <40, lupus anticoagulant (Russell viper venom method) 34.5 seconds pre-neutralization and 29.2 seconds post-neutralization, anti-cardiolipin immunoglobulin G 1 U/mL, and negative detection of severe acute respiratory syndrome coronavirus 2 by loop-mediated isothermal amplification test. Magnetic resonance (MR) imaging showed contrast defects in the right transverse sinus extending into the sigmoid sinus on contrast-enhanced T1-weighted images (Fig. 1A-C). MR venography demonstrated poor visualization from the right transverse sinus to the sigmoid sinus (Fig. 1D). MR angiography detected no evidence of DAVF (Fig. 1E). Based on these findings, the patient was diagnosed with CVST and secondary intracranial hypertension. Anticoagulant therapy was initiated with continuous intravenous heparin for 1 week, followed by oral edoxaban 60 mg. Acetazolamide was also prescribed to control intracranial pressure. After treatment, the patient's headache improved, but his vision gradually worsened, and he developed blurred vision. One month later, he began experiencing pulsatile tinnitus. Four months after the initial treatment, MR angiography suggested the presence of a DAVF in the right transverse sinus (Fig. 1F), and the patient was referred to our department.
A-C: Gadolinium-enhanced T1-weighted imaging at the time of CVST showed contrast defects in the right transverse-sigmoid sinus and the jugular vein (arrowhead). D: MR venography at diagnosis of CVST showed severe stenosis of the right transverse-sigmoid sinus (arrowhead). E, F: MR angiography at diagnosis of CVST (E) revealed no evidence of dural arteriovenous fistula, but some feeders from the middle meningeal artery to the right transverse sinus (arrowhead) were evident after 4 months (F).
CVST: cerebral venous sinus thrombosis; MR: magnetic resonance
On admission, the patient was conscious and alert, and complained of headache, bilateral blurred vision, and pulsatile tinnitus. Visual acuity testing revealed deterioration compared to the initial findings, with corrected visual acuity of 0.3/0.2 in the right and left eyes. Fundoscopy showed bilateral papilledema, although this had improved since the initial examination.
Cerebral angiography revealed that the main feeders of the DAVF in the right transverse sinus were the posterior convexity branch (PCB) and petrosquamous branch of the right middle meningeal artery (MMA); the stylomastoid branch, mastoid branch and dural branches of the right occipital artery; and the neuromeningeal branch of the right ascending pharyngeal artery. The DAVF formed a shunt at the site where the vein of Labbé entered the right transverse sinus, with no drainage into the venous sinus and directly draining only into the right vein of Labbé. The DAVF was diagnosed as the on-the-wall type, Cognard type IIb (Fig. 2A). In the venous phase, the right jugular vein was occluded (Fig. 2B). Edoxaban administration was discontinued based on the aggressive nature of this DAVF, characterized by cortical venous reflux and the associated risk of intracranial hemorrhage.
A, B: DSA before the first TAE. Right external carotid artery angiography in the arterial phase (A) demonstrated multiple arterial feeders to the transverse sinus (arrowhead), including the occipital artery, ascending pharyngeal artery, and MMA, and in the venous phase (B) demonstrated occlusion of the right jugular vein. C: Right external carotid artery angiography after the first TAE demonstrated MMA shunts directly to the vein of Labbé (arrowhead). D: Plain craniography after the first TAE demonstrating the Onyx cast in the transverse sinus and the vein of Labbé. E, F: DSA before the second TAE. Right external carotid artery angiography (E) demonstrated MMA shunts directly to the vein of Labbé (arrowhead), similar to the findings immediately after the first TAE. Right internal carotid artery (F) demonstrated some middle cerebral artery shunts directly to the vein of Labbé (arrowhead). G, H: DSA after the second TAE. Right external (G) and internal (H) carotid artery angiography demonstrated no residual shunts. I: Plain craniography after the second TAE demonstrated that the Onyx cast extended further distally from the transverse sinus to the vein of Labbé compared to after the first TAE.
DSA: digital subtraction angiography; MMA: middle meningeal artery; TAE: transarterial embolization
Under general anesthesia, transarterial embolization (TAE) was performed using Onyx (Onyx 18; Medtronic, Irvine, CA, USA) injected via the right MMA PCB, which successfully obliterated the shunt at the vein of Labbé inflow site. However, a residual shunt persisted at the distal end of the formed cast, where direct inflow from the right MMA PCB into the vein of Labbé occurred at the convexity dura (Fig. 2C and D). Cortical venous reflux into the right vein of Labbé was reduced, so the first treatment session was concluded. Pulsatile tinnitus resolved immediately postoperatively. One month after treatment, papilledema had improved only in the left eye, but visual impairment remained unchanged. Follow-up angiography revealed a residual convexity DAVF directly draining into the right vein of Labbé, with the right MMA PCB as the main feeder, similar to the findings at the conclusion of the first treatment session (Fig. 2E). Additionally, right internal carotid artery (ICA) angiography revealed a pial arteriovenous fistula (PAVF) supplied by the middle temporal artery of the right middle cerebral artery (MCA), draining into the right vein of Labbé (Fig. 2F). Therefore, a second TAE was performed under general anesthesia.
Onyx was injected via 2 feeders from the right MMA PCB, achieving occlusion of the shunt on right external carotid artery angiography (Fig. 2G). Further Onyx injection via the right MCA middle temporal artery resulted in occlusion of the shunt on right ICA angiography (Fig. 2H and I). Postoperatively, the patient's headache and blurred vision gradually improved. Given the improvement in the patient's symptoms, anticoagulant therapy was not resumed, and the patient was managed with careful observation. One month after the second treatment, papilledema had resolved bilaterally, although visual impairment persisted. Ten months later, the patient experienced a recurrence of headache, inability to focus his eyes, and pulsatile tinnitus. Visual acuity testing showed no significant deterioration, with corrected vision of 0.3/0.4 in the right and left eyes, but fundoscopic examination revealed recurrence of bilateral papilledema. MR angiography suggested recurrence of the DAVF (Fig. 3A). Cerebral angiography revealed a newly formed shunt in the convexity dura of the right vein of Labbé, distal to the previous Onyx cast, classified as Cognard type III convexity DAVF (Fig. 3B). The venous phase showed reduced visualization of the right transverse-sigmoid sinus compared to previous studies, and the right jugular vein remained occluded, similar to the initial findings (Fig. 3C). Suspecting recurrence of the DAVF, a third endovascular treatment was performed under general anesthesia.
A: MR angiography 10 months after the second TAE revealed persistent feeders from the MMA to the vein of Labbé (arrowhead). B, C: DSA before the third TAE. Right external carotid artery angiography in the arterial phase (B) demonstrated MMA shunts directly to the vein of Labbé (arrowhead), and in the venous phase (C) demonstrated right severe stenosis of the transverse and sigmoid sinus and occlusion of the right jugular vein. D: Right external carotid artery angiography after the third TAE demonstrated no residual shunts. E: Plain craniography after third TAE demonstrated that the Onyx cast extended further distally from the transverse sinus to the vein of Labbé compared to after the second TAE.
DSA: digital subtraction angiography; MMA: middle meningeal artery; MR: magnetic resonance; TAE: transarterial embolization
Percutaneous transluminal angioplasty of the right jugular vein was attempted but was unsuccessful, as the device could not be guided beyond the occlusion. Therefore, TAE was performed. Onyx was injected via the 2 feeders from the right MMA PCB, successfully obliterating the shunt (Fig. 3D and E). Edoxaban 60 mg administration was resumed postoperatively. The patient's pulsatile tinnitus resolved immediately after the procedure, and his headache and visual symptoms gradually improved. One month postoperatively, papilledema had resolved bilaterally. At 6 months after treatment, corrected visual acuity had improved to 0.3/0.5 in the right and left eyes, and further improved to 0.6/1.0 at 12 months. By 18 months after treatment, corrected visual acuity had fully recovered to 1.0 bilaterally, and no recurrence of the DAVF was observed.
The mechanism by which CVST leads to the development of DAVF has been suggested to involve the organization of a thrombus within the venous sinuses, resulting in arteriovenous shunts which lead to the DAVF, or development of the DAVF as an alternative drainage route in response to elevated venous pressure.3) The incidence of DAVF following CVST was reported as 1.2% among 77 patients during a mean follow-up period of 77.8 months,4) and 4.9% among 308 patients during a follow-up period of 20 to 365 days.5) On the other hand, the incidence was recently reported as 27.8% during a mean follow-up period of 4.8 years,6) which could be attributed to improvements in MR imaging/MR angiography resolution and the introduction of new imaging sequences. The characteristics of CVST preceding DAVF include persistence of thrombus within the venous sinus, or changes in occlusion pattern due to additional thrombus formation and obstructive mechanisms in the chronic phase.6-8) In the present case, initial cerebral angiography revealed that the right transverse-sigmoid sinus was visualized, but thrombi remained within the sinus and the right internal jugular vein was occluded. The DAVF was treated in 2 sessions, but recurred 10 months later. Cerebral angiography at the time of recurrence showed that the right transverse-sigmoid sinus was no longer visible, suggesting that further thrombus formation in the chronic phase may have caused the recurrence of DAVF.
Various characteristics of DAVF secondary to CVST have been reported. The most common locations of the DAVFs are the transverse-sigmoid sinus and the superior sagittal sinus,5,9,10) and 47% of cases were Cognard type I, 20% were type IIa, 6.7% were type IIb, 6.7% were type III, and 20% were type IV.5) Type I accounted for approximately half of the cases, but many were also associated with cortical venous reflux. Additionally, multiple and complex lesions may occur. Two of 245 DAVF cases were secondary to CVST, and both were located in the convexity.9) CVST can lead to multiple DAVFs.11) Furthermore, CVST can lead to DAVF and PAVF simultaneously.12) In the present case, the DAVF in the transverse sinus was complicated by convexity DAVF and PAVF, which is consistent with the reported characteristics of DAVF after CVST.
The major COVID-19 vaccines currently in use can be categorized into adenovirus vector vaccines, such as the Oxford-AstraZeneca (AZD1222 [ChAdOx1]) vaccine and the Johnson & Johnson COVID-19 (JNJ-78436735 [Ad26.COV2.S]) vaccine, and mRNA vaccines, such as the Moderna (mRNA-1273) vaccine and the Pfizer/BioNTech (BNT162b2) vaccine. The mechanism of CVST has been reported to differ between adenovirus vector and mRNA vaccines.13) CVST following adenovirus vector vaccination is regarded as a condition similar to heparin-induced thrombocytopenia (HIT),14,15) and occurs 4 to 28 days after vaccination. The laboratory findings are characterized by thrombocytopenia, abnormalities in coagulation markers, and positivity for platelet factor 4 (PF4) antibodies. The proposed mechanism, similar to autoimmune HIT, involves a complex between PF4 and polyanions (such as heparin analogs) or free deoxyribonucleic acid present in the vaccine. The antibodies produced against this complex may activate platelets, leading to thrombosis.15) Intravenous immunoglobulin therapy and anticoagulation are reported to be effective following the approach used for autoimmune HIT.16) On the other hand, CVST following mRNA vaccination has been reported to occur 1 to 10 days post-vaccination, typically without accompanying thrombocytopenia or positivity for PF4.17-19) The proposed mechanism involves the activation of the complement pathway by mRNA binding to the receptors involved in the inflammatory cascade prior to the translation of the spike protein, potentially leading to thrombosis. A case of DAVF occurred following CVST after COVID-19 vaccination with mRNA vaccine, and thrombocytopenia was not observed.17) The DAVF involved the transverse sinus and the convexity, presenting as a multifocal case. The patient was treated with TAE, but recurrence occurred 2 months later, necessitating a second TAE. The present case was characterized by the development of CVST following mRNA vaccination, subsequent DAVF, absence of thrombocytopenia, involvement of both the transverse sinus and convexity in the DAVF, and recurrence after TAE, all of which are consistent with the previously reported features.
The recommended treatment of CVST is anticoagulation therapy (such as heparin or warfarin) according to the guidelines issued by the American Heart Association/American Stroke Association in 2011 and the European Stroke Organization in 2015.20,21) The present case occurred before publication of the report suggesting that a HIT-like pathophysiology may be involved as a complication of CVST following COVID-19 vaccination. Retrospectively, the use of heparin could have risked worsening the condition; however, heparin was administered in the acute phase in accordance with the above guidelines. It is important to note that CVST following mRNA vaccination typically involves normal platelet counts and is often negative for PF4, unlike CVST following adenovirus vector vaccination, which often presents with a HIT-like pathophysiology. Therefore, heparin will not necessarily exacerbate the condition in such cases. Direct oral anticoagulants (DOACs) are safe and effective treatment options for CVST, as shown in a randomized trial comparing dabigatran with warfarin and a meta-analysis comparing warfarin with DOACs.22,23) Consequently, DOACs are considered an effective treatment option. Additionally, the World Health Organization interim guidelines propose DOACs as the first-line anticoagulant therapy for CVST following COVID-19 vaccination.24) In the present case, heparin was administered during the acute phase of CVST, followed by a switch to the DOAC edoxaban 1 week later. Following the development of the DAVF, edoxaban administration was discontinued before the first endovascular treatment. Additional thrombus formation was observed in the right transverse-sigmoid sinus at recurrence, indicating worsening of CVST. After the endovascular procedure successfully occluded the shunt, edoxaban administration was reinitiated. Symptoms such as visual disturbances gradually improved, and DAVF had not recurred at 18 months after the re-treatment. Based on the recurrence of DAVF during the period of discontinuation of edoxaban and the absence of recurrence after resumption, anticoagulant therapy may be important for preventing recurrence inpatients with DAVF related to sinus occlusion. Therefore, continuation or discontinuation of anticoagulant therapy should be carefully considered in such cases.
CVST associated with COVID-19 vaccination may progress to DAVF, which can recur and may require multiple treatments. Therefore, careful monitoring with imaging is essential. Furthermore, anticoagulant therapy may be important to prevent recurrence.
The authors would like to thank Aries Publications Support for the English language review.
Informed consent has been obtained from the patient for this report.
All authors have no conflict of interest.
