Acute management of cerebral venous thrombosis: Indications,technique,and outcome of endovascular treatment in two high-volume centers

Abstract

Introduction

After several uncontrolled studies and one randomized clinical trial, there is still uncertainty regarding the role of endovascular treatment (EVT) in cerebral venous thrombosis (CVT). This study aims to describe and assess different acute management strategies in the treatment of CVT.

Methods

We performed a retrospective analysis of an international two-center registry of CVT patients admitted since 2019. Good outcome was defined as a return to baseline modified Rankin scale at three months. We described and compared EVT versus no-EVT patients.

Results

We included 61 patients. Only one did not receive systemic anticoagulation. EVT was performed in 13/61 (20%) of the cases, with a median time from diagnosis to puncture of 4.5 h (1.25–28.5). EVT patients had a higher median baseline NIHSS [6 (IQR 2–17) vs 0 (0–2.7), p = 0.002)] and a higher incidence of intracerebral hemorrhage (53.8% vs 20.3%, p = 0.03). Recanalization was achieved in 10/13 (77%) patients. Thrombectomy was performed in every case with angioplasty in 7 out of 12 patients and stenting in 3 cases. No postprocedural complication was reported. An improvement of the median NIHSS from baseline to discharge [6 (2–17) vs 1(0–3.75); p < 0.001] was observed in EVT group. A total of 31/60 patients (50.8%) had good outcomes. Adjusting to NIHSS and ICH, EVT had a non-significant increase in the odds of a good outcome [aOR 1.42 (95%CI 0.73–2.8, p = 0.307)].

Conclusions

EVT in combination with anticoagulation was safe in acute treatment of CVT as suggested by NIHSS improvement. Selected patients may benefit from this treatment.

Keywords

Thrombectomy venous thrombosis intracranial thrombosis cerebral venous sinus thrombosis

Introduction

Cerebral venous thrombosis (CVT) is a subtype of stroke that mainly affects young individuals and has a low incidence. It exhibits a distinct range of symptoms such as headaches, focal neurological deficits, altered mental status, or seizures,^1,2 making it challenging to diagnose early.

Generally, it has a favorable prognosis, as most of the patients remain independent after the acute phase. However, around 20% of patients are disabled or dead and more than half may experience long-term significant sequelae such as headache, visual and cognitive impairment.^3,4

The standard clinical care of patients with CVT is the anticoagulation therapy even in cases of intracranial hemorrhage.² Current guidelines from Europe and America suggest utilizing endovascular treatment (EVT) only when anticoagulation fails to improve the situation.^5,6 Nevertheless, delaying EVT can lead to decreased efficacy and increased difficulty.

Thus far, only a single randomized controlled trial has examined the impact of EVT in conjunction with optimal medical care on severe cases of CVT.⁷ This trial included a mere 67 participants across eight centers and was halted early due to a lack of efficacy. Consequently, questions remain regarding the effectiveness of EVT in this condition, as well as the most effective procedural approach and indications.

This study aimed to assess EVT's efficacy and safety in a two-center cohort of patients with CVT.

Methods

Study design

We performed an international retrospective observational cohort study of two large-volume comprehensive stroke centers. We included consecutive patients admitted from 2019 to early 2023 diagnosed with CVT. All patients were informed of data collection for clinical studies and were free to withdraw consent. Local ethics committee approval was obtained.

Data collection

We collected information about patients’ demographics, medical history, National Institute of Health Stroke Scale (NIHSS), and modified Rankin Scale (mRS) scores before and after treatment. We also noted time metrics, imaging features like the presence of venous infarction or hemorrhage, and thrombosed veins/sinus, as well as treatment and procedural approaches. All patients in both institutions underwent non-contrast CT scans followed by CT venograms. The neurologist, and neurointerventionalist decided to perform EVT for CVT at their discretion. Endovascular techniques included mechanical thrombectomy (aspiration and/or stent-retriever) angioplasty and stenting. Recanalization was assessed at the end of the procedure and defined as a significant improvement of blood flow to an occluded sinus accompanied by enhanced cerebral venous drainage. A good outcome was defined as a return to baseline mRS after 3 months. mRS scores at one year were also collected when available. Electronic medical records were used.

Data analysis

Categorical variables are presented as absolute values (percentages), and continuous variables are presented as means ± SD or medians (interquartile intervals). Normality of continuous variables was evaluated through histogram and Kolmogorov–Smirnoff tests. For categorical variables, intergroup statistical significance was assessed using the Pearson χ² test. The appropriate tests such as Mann–Whitney U-test, Kruskal–Wallis, and Wilcoxon signed rank test were employed for continuous variables.

We conducted a descriptive analysis of our study sample and evaluated the EVT strategies employed. Group comparisons were made between patients who underwent EVT and those who did not. We used propensity score-based inverse probability of treatment weighting (IPTW) method to adjust for confounders and estimate the average treatment effect of EVT. We first estimated the probability of EVT based on the presence of confounders (propensity score). Then, the EVT group received weights of [proportion of patients receiving EVT/propensity score], and MM received weights of [proportion of patients receiving MM/(1−propensity score)] as published elsewhere.⁸

Results

A total of 61 patients were included in the study sample (44/61 [71.6%] women; mean ± SD age, 51.6 ± 14 years). The most common symptom was headache in 45 (73.8%) patients, followed by impaired consciousness in 16 (26.2%) patients. The median NIHSS was 1(0–6). Regarding CT findings, 18 patients (29.5%) had a venous infarction, and 17 (27.9%) had an intracerebral hemorrhage in the admission head CT. The most affected venous sinuses were the transverse sinus (48 patients, 75.4%), sigmoid sinus (46 patients, 754%), and superior sagittal sinus (33 patients, 54.1%). A total of 60 (99%) patients received systemic anticoagulation with heparin (12/60 with unfractionated heparin) upon admission. Thirteen patients (20%) underwent EVT. Table 1 compares patients with and without EVT. EVT patients had a higher baseline NIHSS (6 (2–17) vs 0 (0–2.7), p = 0.002) and higher incidence of intracerebral hemorrhage (53.8% vs 20.3%, p = 0.03) in comparison with patients without EVT. EVT was performed with a median (IQR) time from symptom to puncture of 28 h (4.5–94). In six patients (46%) a transjugular access was used and a transfemoral access in the remaining seven patients. Aspiration with large bore catheters was performed in all cases, with a super large bore (088″ or over inner lumen) being used in 8 cases. Angioplasty was used in 7 out of 13 patients and stenting in 3 out of 13 patients. Figure 1 shows one patient submitted to stenting. Figure 2 displays a patient that underwent aspiration-only thrombectomy. The median (IQR) time from diagnosis to puncture was 4.5 h (1.25–28.5). Recanalization was achieved in 10 out of 13 patients (77%), with a median time from puncture to recanalization of 90 (74.3–157.5) minutes. No postprocedural complication was observed. Patients that underwent angioplasty and/or stenting (7/13) had a higher median time from symptom to puncture [76 h (31–144) vs 3.5 h (3–19.75), p = 0.02]. Supplemental Table 1 details each EVT patient and thrombectomy setup. Regarding clinical outcome, we found a significant improvement from baseline to discharge median NIHSS [6 (2–17) vs 1(0–3.75) p < 0.001] in patients submitted to EVT (Figure 3). At three months, 31/61 (50.8%) patients returned to baseline mRS. Even though EVT patients had higher rates of ICH and higher NIHSS, 4/13 (30.8%) of EVT patients returned to baseline mRS and 8/13 (61.5%) were independent (mRS 0–2) at three months. In an IPTW model adjusted to NIHSS and the presence of ICH, EVT had a non-significant increase in the odds of returning to baseline mRS at three months [aOR 1.42 (95%CI 0.73–2.8, p = 0.307)].

Table 1.

Comparison of patients submitted to endovascular treatment with those without endovascular treatment.

	All patients (n = 61)	No-EVT (n = 48)	EVT (n = 13)	p
Age (mean, SD)	46 (21.0)	46 (20.1)	63 (28.6)	0.275
Female sex (n, %)	44(72.1)	34 (70.8%)	10 (76.9%)	1.00
Headache	46(75.4%)	36 (75.0%)	10 (76.9%)	1.00
Seizure	7(11.5%)	4 (8.3%)	3 (23.1%)	0.16
Impaired consciousness	16(26.2%)	10 (20.8%)	6 (46.2%)	0.08
Aphasia	5(8.2%)	3 (6.3%)	2 (15.4%)	0.29
Motor symptoms	16(26.2%)	11 (22.9%)	5 (8.2%)	0.30
Time symptom-diagnosis (h; median, IQR)	12 (3–72)	24 (8–72)	5.5 (1.25–60)	0.13
Baseline NIHSS (median, IQR)	1 (0–6)	0 (0–2.7)	6 (2–17)	<0.001
Basal mRS (median, IQR)	0 (0–0)	0 (0–0)	0(0–1)	0.99
SBP (median, IQR)	132 (107–153)	133 (104–153)	127 (102–161)	0.06
DBP (median, IQR)	81 (56–98)	81 (58–99)	81 (55–97)	0.15
Glucose (median, IQR)	107 (92–132)	102 (92–132)	109(97–122)	0.27
D-Dimer (median, IQR)	295 (248–484)	277 (201–440)	484 (381–617)	0.10
Ischemia on NCCT	18 (29.5%)	12 (25%)	6 (46.2%)	0.18
Hemorrhage on NCCT	17(27.6%)	10 (20.8%)	7 (53.8%)	0.03
Superior sagittal sinus thrombosis	33 (54.1%)	23 (47.9%)	10 (30.3%)	0.12
Straight sinus thrombosis	14(23.0%)	9 (18.8%)	5 (38.5%)	0.15
Transverse sinus thrombosis	48 (78.7%)	37 (77.1%)	11 (84.6%)	0.72
Sigmoid sinus thrombosis	46 (75.4%)	36 (75.0%)	10 (76.9%)	1.00
Jugular vein thrombosis	35(57.4%)	28 (58.3%)	7 (53.8%)	1.00
Deep venous system thrombosis	9 (14.8%)	5 (10.4%)	4 (30.8%)	0.09
Discharge NIHSS (median, IQR)	0 (0–1)	0 (0–1)	1 (0–4)	0.03
Discharge mRS (median, IQR)	1 (0–1)	1 (0–1)	3 (1–4.5)	0.02
3-month mRS (median, IQR)	1 (0–2)	1 (0–1)	2 (0–3)	0.06
mRS 0–2 (n,%)	51 (83.6%)	43 (89.6%)	8 (61.5%)	0.03
Return to baseline mRS (n, %)	31 (50.8%)	27 (56.3%)	4 (30.8%)	0.13
1-year mRS^a (median, IQR)	1 (0–1)	0 (0–1)	1 (0–3)	0.75
Mortality (n, %)	3 (4.9%)	2(4.2%)	1(7.7%)	0.52

EVT: endovascular treatment; SD: standard deviation; h: hours; IQR: interquartile range; SBP: systolic blood pressure; DBP: diastolic blood pressure; NCCT: non-contrast head CT scan.

Data unavailable in 3 patients, 1 in EVT group and 2 in no-EVT group.

Discussion

In our 61 patient CVT cohort we found that only half returned to baseline mRS at 3 months. Likewise, a large multicenter 624 CVT patient follow-up study⁹ showed that only 57.1% had a mRS of 0. Our results are consistent with published data on the long-term outcome of CVT which is frequently associated with persistent residual symptoms such as headache, cognitive impairment and depression⁴ that render a mRS of 0 or a return to baseline mRS unattainable. Since every patient except for one received parenteral anticoagulation and the outcome was suboptimal, other treatments beyond the current standard of care are deemed necessary.

Patients submitted to EVT had a higher NIHSS and more ICH reflecting a more severe disease status. ICH has been shown to predispose clinicians to consider endovascular approaches.^10,11 In our cohort, a positive treatment effect of EVT in addition to anticoagulation is supported by the non-significant increase in the odds of achieving a good outcome in patients submitted to EVT and particularly by the statistically significant reduction from baseline to discharge NIHSS in EVT patients. Similar findings in NIHSS reduction were found in a recent single-center case series.¹² The majority of observational studies report on the efficacy of EVT by means of achievement of 0–2 or 0–1 mRS at three months.^11,13–15 This scale may not be sufficient to differentiate clinically important changes beyond motor impairment and is not as granular and sensitive as NIHSS, cognitive scales and patient-related outcome measures to detect treatment effects.¹⁵ Moreover, using a dichotomized mRS as primary outcome measure probably requires too large of a patient sample size to detect a treatment effect, considering CVT incidence.

EVT recanalized more than two-thirds of the patients to whom it was performed. Currently, there is no consensus nor a standardized scale to determine the technical success of EVT in CVT in opposition to the TICI score in ischemic stroke. An incomplete recanalization and a reduction in clot burden may be sufficient to allow venous reflow, reducing intracranial pressure and allowing both autofibrinolysis and systemic anticoagulation to act on the residual clot and potentially avoiding lifelong sequelae.¹⁵ The TO-ACT trial did not even report immediate post-treatment results. A large 185-patient systematic review in the pre-thrombectomy era¹³ reported a 74% rate of near-to-complete recanalization. A more recent thrombectomy-era single-center study with 23 EVTs in CVTs reported a complete recanalization in 8/23 (34.8%) and partial recanalization in 13/23 (56.5%) patients.

In our cohort, patients that underwent angioplasty and/or stenting had higher median times from symptom to puncture. This probably reflects the fact that, with time, a thrombus in the cerebral venous system progressively becomes more organized, adherent and resistant to thrombectomy, resulting in the need to use reconstructive techniques. Even though recent multicenter observational data¹⁶ present median times from symptom to treatment of 3(2–7) days, the success of EVT may decrease with time as it has been suggested.¹⁵ This means that EVT should be considered early after its diagnosis by an accurate and timely identification of those that may benefit from it.

In our EVT cohort in which every except one patient was under anticoagulation no procedural or postprocedural complications were observed. In TO-ACT trial, mortality and symptomatic intracranial hemorrhage (sICH) were not statistically different in intervention and control groups and only 1/33 (3%) patient in the intervention group developed a sICH, 3/34 (9%) patients in the control group. In 3/33 (10%), a presumable thrombosed cortical vein was perforated. Data from observational studies show possible complications such as new or worsening of ICH^11,13 that may be related to the disease itself and not treatment-related, subarachnoid hemorrhage,¹¹ anemia due to the aspiration of considerable amounts of blood through large bore aspiration catheters¹⁴ and venous access local complication.^13,17 None of the above complications was found in our cohort.

Large or super-large bore aspiration catheters were used in all cases. Large bore catheters have been suggested to be safe and effective in CVT.^14,18 In our series, we used super-large bore catheters in 8 of the 13 cases with a successful recanalization except for one patient. Super large bore catheters (inner diameter of 0.088″) have been recently described to be efficacious in large vessel occlusion acute ischemic stroke particularly in achieving first pass effect.¹⁹ Since superior sagittal sinus has a lumen diameter that ranges from 4 to 10 mm,²⁰ in contrast with the average 3 mm diameter of the middle cerebral artery,²¹ the largest available aspiration catheters with sufficient navigability should theoretically be used to exponentiate clot ingestion. In our series, super large bore catheter aspiration were combined with the largest available 6 and 6.5 mm stent retrievers due to the same anatomical reason for the purpose of anchoring and delivery of aspiration catheter and enhancing clot retrieval. A higher rate of recanalization compared with previous studies may be related with the use of combined technique joined to the effect of new devices designed to retrieve large intraarterial thrombus.^11,17

The usage of EVT is low, as a recent study reported only 1.56% out of 85,370 CVT patients being submitted to this treatment.²² The vast majority of the literature on the efficacy and safety of EVT in CVT was published before the explosion of thrombectomy in arterial stroke and before the TO-ACT trial in 2020 whose neutral findings may have been discouraging clinicians from considering this treatment. Moreover, most studies do not present control groups and therefore do not allow for an estimation of the treatment effect of this intervention.¹¹ Our CVT cohort allows for such estimation and presents data on the outcome of patients treated with and without endovascular techniques.

Several limitations of our study are noteworthy. Our cohort is limited by the small number of EVT patients and the imbalanced groups. The decision to perform EVT and techniques pursued were not standardized and were based on the judgment of the neurologist and interventionalist on call. Other potentially relevant clinical and imaging endpoints beyond angiographic recanalization and 3 months mRS were not studied.

Conclusion

To conclude, EVT with current techniques in combination with anticoagulation is safe as measured by NIHSS improvement and may be considered a treatment option even before the worsening of patients under medical therapy. The number of patients and heterogeneity of symptoms may make randomized data difficult to support endovascular management.

Supplemental Material

sj-docx-1-ine-10.1177_15910199241236819 - Supplemental material for Acute management of cerebral venous thrombosis: Indications, technique, and outcome of endovascular treatment in two high-volume centers

Supplemental material, sj-docx-1-ine-10.1177_15910199241236819 for Acute management of cerebral venous thrombosis: Indications, technique, and outcome of endovascular treatment in two high-volume centers by João André Sousa, Maider Iza Achutegui, Jesus Juega-Mariño, Manuel Requena, Sara Bernardo-Castro, Marc Rodrigo-Gisbert, Federica Rizzo, Marta Olivé, Álvaro Garcia-Tornel, Ana Carolina Chaves, Noelia Rodriguez-Villatoro, Marian Muchada, Jorge Pagola, David Rodriguez-Luna, Marta Rubiera, Ana Inês Martins, Fernando Silva, Ricardo Veiga, Cesar Nunes, Egídio Machado, Francesco Diana, Marta de Dios, David Hernández, Marc Ribo, Carlos Molina, João Sargento-Freitas and Alejandro Tomasello in Interventional Neuroradiology

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

João André Sousa

Manuel Requena

Sara Bernardo-Castro

Francesco Diana

Alejandro Tomasello

Supplemental material

Supplemental material for this article is available online.

References

Ferro

Aguiar de Sousa

. Cerebral venous thrombosis: an update. Curr Neurol Neurosci Rep 2019; 19: 74.

Ropper

Klein

. Cerebral venous thrombosis. N Engl J Med 2021; 385: 59–64.

Koopman

Uyttenboogaart

Vroomen

, et al. Long-term sequelae after cerebral venous thrombosis in functionally independent patients. J Stroke Cerebrovasc Dis 2009; 18: 198–202.

Hiltunen

Putaala

Haapaniemi

, et al. Long-term outcome after cerebral venous thrombosis: analysis of functional and vocational outcome, residual symptoms, and adverse events in 161 patients. J Neurol 2016; 263: 477–484.

Ferro

Bousser

Canhão

, et al. European stroke organization guideline for the diagnosis and treatment of cerebral venous thrombosis - endorsed by the European academy of neurology. Eur Stroke J 2017; 2: 195–221.

Saposnik

Barinagarrementeria

Brown

, 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: 1158–1192.

Coutinho

Zuurbier

Bousser

, et al. Effect of endovascular treatment with medical management vs standard care on severe cerebral venous thrombosis: the TO-ACT randomized clinical trial. JAMA Neurol 2020; 77: 966–973.

Austin

Stuart

. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med 2015; 34: 3661–3679.

Ferro

Canhão

Stam

, et al. 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.

10.

Paybast

Mohamadian

Emami

, et al. Safety and efficacy of endovascular thrombolysis in patients with acute cerebral venous sinus thrombosis: a systematic review. Interv Neuroradiol 2022: 15910199221143418.

11.

Bücke

Hellstern

Cimpoca

, et al. Endovascular treatment of intracranial vein and venous Sinus thrombosis—A systematic review. J Clin Med 2022; 11: 4215.

12.

Piano

Romi

Cervo

, et al. Endovascular treatment of cerebral vein thrombosis: safety and effectiveness in the thrombectomy era. Diagnostics (Basel) 2023; 13: 2248.

13.

Siddiqui

Dandapat

Banerjee

, et al. Mechanical thrombectomy in cerebral venous thrombosis: systematic review of 185 cases. Stroke 2015; 46: 1263–1268.

14.

Dandapat

Samaniego

Szeder

, et al. Safety and efficacy of the use of large bore intermediate suction catheters alone or in combination for the treatment of acute cerebral venous sinus thrombosis: a multicenter experience. Interv Neuroradiol 2020; 26: 26–32.

15.

Goyal

Fladt

Coutinho

, et al. Endovascular treatment for cerebral venous thrombosis: current status, challenges, and opportunities. J Neurointerv Surg 2022; 14: 788–793.

16.

Siegler

Shu

Yaghi

, et al. Endovascular therapy for cerebral vein thrombosis: a propensity-matched analysis of anticoagulation in the treatment of cerebral venous thrombosis. Neurosurgery 2022; 91: 749–755.

17.

Ilyas

Chen

Raper

, et al. Endovascular mechanical thrombectomy for cerebral venous sinus thrombosis: a systematic review. J Neurointerv Surg 2017; 9: 1086–1092.

18.

Kothari

Morsi

Thind

, et al. Endovascular thrombectomy for cerebral venous sinus thrombosis using the penumbra Indigo® aspiration system. Interv Neuroradiol 2023: 15910199231152692.

19.

Massari

Dabus

Cortez

, et al. Super large-bore ingestion of clot (SLIC) leads to high first pass effect in thrombectomy for large vessel occlusion. J Neurointerv Surg 2023; 15: 664–668.

20.

Curé

Tassel

Smith

. Normal and variant anatomy of the dural venous sinuses. Seminars in ultrasound. CT and MRI 1994; 15: 499–519.

21.

Rai

Hogg

Cline

, et al. Cerebrovascular geometry in the anterior circulation: an analysis of diameter, length and the vessel taper. J Neurointerv Surg 2013; 5: 371–375.

22.

Wahood

Rizvi

Patel

, et al. Trends in utilization and outcomes of mechanical thrombectomy for cerebral venous thrombosis: a national inpatient sample study. Interv Neuroradiol 2023: 15910199231182454.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.02 MB