Local Thrombolysis Combined with Balloon Dilation for Patients with Severe Cerebral Venous Sinus Thrombosis
Cerebral venous sinus thrombosis (CVST) is a rare but serious condition characterized by the formation of blood clots in the cerebral veins and sinuses. If not treated promptly and effectively, CVST can lead to severe consequences such as intracranial hypertension, cerebral venous infarcts, epilepsy, significant neurological morbidity, and even death. The standard treatment for CVST involves anticoagulation therapy using unfractionated heparin or low-molecular-weight heparin (LMWH). While anticoagulation has significantly reduced mortality rates, 5% to 30% of patients still die from CVST each year. For patients who do not respond to systemic anticoagulation, endovascular treatment is considered as an alternative.
Endovascular treatment for CVST primarily includes two techniques: local thrombolysis, which involves the infusion of thrombolytic drugs directly into the thrombus, and mechanical thrombectomy, which uses specialized devices to remove the clot. In some cases, these two methods are combined. Local thrombolysis offers the advantage of precise drug delivery, while balloon dilation can theoretically accelerate thrombus dissolution by breaking it apart. However, the safety and efficacy of combining balloon dilation with local thrombolysis remain uncertain.
This study aimed to evaluate the effectiveness and safety of combined balloon dilation and local thrombolysis in patients with severe CVST who were refractory to heparin treatment. The study included 40 patients admitted to the Second Affiliated Hospital of Zhejiang University School of Medicine between October 2015 and November 2019. The diagnosis of CVST was confirmed using contrast-enhanced magnetic resonance venography (CEMRV). All patients initially received subcutaneous LMWH as anticoagulation therapy. Endovascular treatment was considered for patients who showed no improvement or experienced progressive neurological deterioration despite adequate anticoagulation. The study was approved by the Ethics Committee of the hospital, and informed consent was obtained from the patients’ relatives.
The endovascular procedure involved a combination of balloon dilation and local thrombolysis. Under local or general anesthesia, a 6F 90-cm shuttle sheath was inserted percutaneously from the femoral vein to the jugular bulb. A Rebar microcatheter was then advanced into the superior sagittal or straight sinus using a 300-cm, 0.014-inch guide wire. A 4 mm × 20 mm rapid exchange dilatation catheter was inserted into the thrombotic venous sinus and inflated repeatedly to crush the thrombus. Following balloon dilation, the Rebar microcatheter was reinserted, and a solution of 500,000 U of urokinase in 48 mL of normal saline was continuously infused at a rate of 4 mL/h. Urokinase infusion continued at a dose of 1,000,000 U/day until the microcatheter was removed. Direct venous sinus angiograms were performed every 2 or 3 days to monitor progress. Thrombolysis was discontinued if the venous sinus became patent, if active bleeding occurred, if clinical symptoms improved without venous sinus patency after 7 days, or if the patient’s condition deteriorated irreversibly.
During the procedure, dilute heparin was continuously infused through the shuttle sheath, with the dosage adjusted to maintain an activated partial thromboplastin time of 60 to 90 seconds. Postoperative CEMRV was performed to assess short-term outcomes before discharge. All patients were subsequently prescribed long-term oral anticoagulation with warfarin, adjusted to maintain an international normalized ratio of 2–3.
Patients were followed up for 3 to 6 months via outpatient visits or telephone calls. Sinus recanalization was evaluated using CEMRV at the 3-month mark. Clinical outcomes were assessed using the modified Rankin scale (mRS), with treatment response categorized as satisfactory improvement (mRS scores of 0, 1, or 2), partial improvement (mRS scores of 3 or 4), or poor outcome (mRS scores of 5 or 6).
The study included 40 patients with a mean age of 37.9 ± 14.6 years (range: 16–67 years). The median time from symptom onset to diagnosis was 7 days (range: 3–360 days), and the median time from diagnosis to anticoagulation was 0 days (range: 0–6 days). The median time from anticoagulation to thrombolysis was 4 days (range: 0–170 days). Before endovascular treatment, 16 patients had disturbed consciousness (stupor or coma), 17 had tonic-clonic seizures, and 21 had intracranial hemorrhage.
The technical success rate for catheterization was 100% (40/40). Balloon dilation was performed in 38 patients, with no operation-related complications reported. Thirty-two patients received endovascular treatment within 30 days of symptom onset, and the microcatheter was successfully inserted into the superior sagittal or straight sinus for thrombolysis in all cases. Eight patients received treatment beyond 30 days, with three undergoing successful thrombolysis and five unable to reach the target position. Overall, 35 patients underwent local thrombolysis, with a median thrombolysis duration of 5 days (range: 1–7 days).
Thrombolytic therapy was terminated early in three patients: two due to rapid deterioration leading to death and one due to bleeding on the floor of the mouth. Postoperative CEMRV in 38 patients showed complete recanalization in 36.8% (14/38), partial recanalization in 57.9% (22/38), and no change in 5.3% (2/38). Among the 33 patients treated with the combined technique, complete recanalization was observed in 42.4% (14/33) and partial recanalization in 57.6% (19/33).
All patients required oral anticoagulants for at least 6 months post-discharge. At follow-up, 35 patients had no residual symptoms (mRS scores of 0 or 1), and three had moderate disability (mRS score of 3). CEMRV at 3–6 months revealed complete recanalization in 86.8% (33/38), partial recanalization in 7.9% (3/38), and no change in 5.3% (2/38). All 33 patients treated with the combined technique achieved complete recanalization.
The study demonstrated that combined balloon dilation and local thrombolysis is a safe and effective treatment for severe CVST. The mortality rate in this study was 5.0% (2/40), and 87.5% (35/40) of patients achieved satisfactory recovery (mRS scores of 0 or 1). The findings suggest that intraoperative complete recanalization is not necessary for a good clinical outcome, as favorable results were observed even with partial recanalization. The absence of operation-related complications highlights the safety of the procedure.
Comatose status was identified as a significant prognostic factor for poor outcomes. In this study, 16 patients were comatose before endovascular treatment, and two died despite the intervention. However, the mortality rate among comatose patients was lower than that reported in studies using conventional anticoagulation alone. This suggests that active endovascular treatment can reduce mortality in severe cases.
Another notable finding was the high incidence of internal jugular venous thrombosis (82.5%) among the study participants, which may serve as an imaging marker for refractory CVST. If jugular venous thrombosis extends from intracranial venous sinus thrombosis, endovascular treatment should be considered promptly.
In conclusion, this study provides evidence supporting the safety and efficacy of combined balloon dilation and local thrombolysis for severe CVST. Comatose status remains a critical prognostic factor, and jugular venous thrombosis may indicate refractory disease. Further research with larger sample sizes is needed to confirm these findings.
doi.org/10.1097/CM9.0000000000001315
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