Mechanical Thrombectomy in Cerebral Venous Thrombosis
Systematic Review of 185 Cases
Background and Purpose—Cerebral venous thrombosis is generally treated with anticoagulation. However, some patients do not respond to medical therapy and these might benefit from mechanical thrombectomy. The aim of this study was to gain a better understanding of the efficacy and safety of mechanical thrombectomy in patients with cerebral venous thrombosis, by performing a systematic review of the literature.
Methods—We identified studies published between January 1995 and February 2014 from PubMed and Ovid. We included all cases of cerebral venous thrombosis in whom mechanical thrombectomy was performed with or without intrasinus thrombolysis. Good outcome was defined as normal or mild neurological deficits at discharge (modified Rankin Scale, 0–2). Secondary outcome variables included periprocedural complications and recanalization rates.
Results—Our study included 42 studies (185 patients). Sixty percent of patient had a pretreatment intracerebral hemorrhage and 47% were stuporous or comatose. AngioJet was the most commonly used device (40%). Intrasinus thrombolysis was used in 131 patients (71%). Overall, 156 (84%) patients had a good outcome and 22 (12%) died. Nine (5%) patients had no recanalization, 38 (21%) had partial, and 137 (74%) had near to complete recanalization. The major periprocedural complication was new or increased intracerebral hemorrhage (10%). The use of AngioJet was associated with lower rate of complete recanalization (odds ratio, 0.2; 95% confidence interval, 0.09–0.4) and lower chance of good outcome (odds ratio, 0.5; 95% confidence interval, 0.2–1.0).
Conclusions—Our systematic review suggests that mechanical thrombectomy is reasonably safe but controlled studies are required to provide a definitive answer on its efficacy and safety in patients with cerebral venous thrombosis.
Cerebral venous thrombosis (CVT) is a rare cause of stroke.1 Anticoagulation is generally accepted as the principal therapy based on data from 2 randomized trials.1–3 However, a subset of patients does not respond to medical therapy.1,2 In those cases, CVT can rapidly progress to cause ischemic and hemorrhagic strokes, cerebral edema and mass effect, and eventually death. In the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT), ≈13% of patients experienced bad outcomes even after treatment with anticoagulation.4 The main predictors of death included rapid clinical deterioration despite anticoagulation, coma, intracerebral hemorrhage (ICH), deep CVT, and posterior fossa involvement.5 Patients with these risk factors may benefit from early and aggressive therapy, such as intrasinus thrombolysis (IST), or mechanical thrombectomy.1,6–10 However, data are clearly lacking about the proper indication and timing of these procedures. Two of the larger prospective studies have used the above-mentioned predictors of death as the criteria to enroll patients in MT group.7,10
The use of IST has shown promise but its efficacy may be limited in patients with high clot burden or extensive involvement of multiple sinuses. Mechanical methods may result in a more rapid recanalization and increase the surface of the thrombus exposed to IST.7 Gurley et al11 reported the first use of MT in CVT using balloon angioplasty. Since then, many different devices have been used for MT in patients with CVT, including AngioJet, Penumbra, Mechanical Embolus Removal in Cerebral Ischemia (MERCI) retriever, and retrievable stents.7,12–14
A potential drawback of MT is that it is not possible to access thrombosed cortical veins because of the risk of perforation. Intracranial hemorrhagic complications have also been reported, because of either perforation or concurrent use of IST. The reported clinical outcomes after MT vary greatly per study, with mortality rates ≤30%.7 Most centers use MT or IST as a last resort. Because of rarity of experience with these procedures, we have little knowledge about the mortality, morbidity, and periprocedural complications associated with these procedures, as most published data come from case reports or small case series. The aim of this study was to gain a better understanding of the efficacy and safety of MT in patients with CVT, by performing a systematic review of the literature.
Materials and Methods
Study Selection Criteria
We searched the literature from January 1, 1995, through February 4, 2014, to identify individual studies, using PubMed (US National Library of Medicine) and Ovid (Wolters Kluwer) databases. The following key words were used for this search: [“thrombectomy”, OR “cerebrum”, OR “brain”] AND [“venous thrombosis”]. We also hand-searched references provided in review articles and textbook chapters on this topic to identify any pertinent studies. We included all cases of CVT in whom MT was performed with or without IST. All types of studies were eligible, including case reports. We excluded studies published in languages other than English.
Using a predefined data abstraction form, 2 investigators independently evaluated all studies and abstracted the following information: study characteristics, patient demographics, baseline clinical and radiological findings, technical details of the endovascular procedure, and clinical outcome. Based on the interval from symptom onset to intervention, we classified cases as acute/subacute (<21 days) or chronic (≥21 days).
Clinical outcome was classified as good (normal or mild neurological deficits at discharge; modified Rankin Scale, 0–2), poor (severe neurological deficits; modified Rankin Scale, 3–5), or death. Other outcome variables of interest were periprocedural complications (defined as complications within 30 days of procedure), new or increased ICH after the procedure and recanalization rate. Recanalization was defined as no recanalization or technical failure, partial or incomplete recanalization (contrast visible but lumen too narrow), and complete or near complete recanalization.
Continuous data are given as weighted mean with SD and categorical variables are presented as n/N (%), where n is the number of patients in which that variable is present and N the total number of patients for which that particular variable was reported. We performed several subgroup analyses with the following predefined outcomes of interest: recanalization (complete versus partial or no recanalization), clinical outcome (modified Rankin Scale, 0–2 versus 3–6), periprocedural ICH, and any periprocedural complication. Univariate associations between each of these outcomes and the following variables were calculated: year of publication (dichotomized at median), year of procedure (dichotomized at median), age (dichotomized at median), mode of presentation (chronic versus acute or subacute), stupor/coma before endovascular procedure, preprocedure ICH, use of AngioJet device, and concurrent IST use. For each association unadjusted odds ratios (ORs) and 95% confidence intervals (CIs) are given.
Our initial search criteria returned 1077 studies from PubMed and 7163 from Ovid (Figure). After excluding articles with irrelevant topics or outcome, reviews, and hand searching references of pertinent studies and review articles, we identified 185 cases of MT from 42 studies published between January 1995 and February 2014. Twenty eight of 42 (66%) were single case reports and only 8 of 42 (19%) included ≥5 patients. The median number of patients per study was 1 (range, 1–52). There was 1 prospective study and 2 retrospective analyses of prospectively maintained databases. We identified no randomized trials. A detailed description of the individual studies and the reference list are provided in Tables I and II in the online-only Data Supplement.
Baseline Clinical and Radiological Manifestations
The mean age of included patients was 35 years and 64% were women (Table 1). Overall, our patient population represented a severe subset of CVT. Out of the available data, 60% of patients had pretreatment ICH, 47% were stuporous or comatose, 37% had seizures, and 59% had focal neurological deficits. In 82% of patients, thrombosis of ≥2 venous sinuses was present. Seventy percent of patients were treated with therapeutic dosage of anticoagulation before the endovascular procedure. However, in 27 patients, no data on anticoagulation were reported.
Technical Details of Endovascular Procedure
The endovascular procedure was performed under general anesthesia in 98% of patients for whom details on anesthesia were reported (Table 2). Intraprocedural heparin was used in 90% of patients, but data on heparin use were missing in 30 patients. Venous access was mostly obtained via a transfemoral or transjugular approach. Device details were not reported in 3 cases. In 93 of 182 (51%) patients, >1 device was used. AngioJet (40%) was the most commonly used device (primary or adjunct) followed by a wire (31%), balloon angioplasty (25%), and Penumbra system (7%). Among the 131 (71%) patients who received concurrent IST, 71% received urokinase and 29% received tissue-type plasminogen activator. In 38% of patients, continuous infusion was used, with an average duration of 32 hours (range, 4–240 hours).
Clinical Outcomes and Complications
The clinical and radiological outcomes and periprocedural complications are listed in Table 3. Overall, 156 (84%) patients had a good outcome, 7 (4%) had a poor outcome, and 22 (12%) died. Of the 22 deaths, 10 patients had worsening of hemorrhage and herniation, 6 patients had no clinical improvement with eventual withdrawal of care, 1 patient had reocclusion of sinuses with clinical worsening and withdrawal of care, 1 patient had cardiac arrest, 1 patient developed sepsis, and 1 patient died from complications of acute renal failure. Cause of death was not reported for 2 patients.
Postprocedure recanalization data were available for 184 patients. Out of these, 5% patients had no recanalization, 21% had partial, and 74% had near to complete recanalization. A periprocedural complication was reported in 48 of 185 (26%) patients. The major periprocedural complication besides death was new or increased ICH, which occurred in 18 patients (10%). Of these, 11 of 18 (61%) were increased size of pre-existing hemorrhages. Nine of these 11 had been treated with concurrent IST.
Patients with pretreatment stupor/coma significantly less often had complete recanalization (OR, 0.3; 95% CI, 0.1–0.6; Table 4). These patients also less often had a good outcome (OR, 0.1; 95% CI, 0.02–0.3) and more often experienced a periprocedural complication (OR, 5.2; 95% CI, 2.3–11.5). Baseline ICH was also associated with a lower chance of good outcome (OR, 0.3; 95% CI, 0.1–0.9). Age, year of procedure or publication, mode of presentation, and use of concurrent IST were all not significantly associated with any of the predefined outcomes. Complete recanalization was association with a good outcome (OR, 4.1; 95% CI, 1.8–9.4) and lower risk of complications (OR, 0.3; 95% CI, 0.2–0.7). The use of the AngioJet device was significantly associated with a lower chance of complete recanalization (OR, 0.2; 95% CI, 0.1–0.4), a lower chance of good clinical outcome (OR, 0.5; 95% CI, 0.2–1.0) and higher risk of periprocedural complications (OR, 2.3; 95% CI, 1.2–4.6).
We performed this analysis to answer few burning questions related to the use of MT in patients with CVT.
What Is the Use and Safety of MT in the Treatment of CVT?
Anticoagulation remains the mainstay treatment for most patients with CVT as MT has procedure-related risks that cannot be ignored. However, anticoagulation may not be the only treatment choice for complicated CVT patients. In patients who show signs of rapid deterioration, MT is technically feasible and has shown benefit with good recanalization rates in different case series and prospective cohorts. However, it remains unknown whether it improves clinical outcome in this subgroup compared with anticoagulation alone. In patients with impending transtentorial herniation, achievement of good recanalization through MT may not be the right answer to prevent death and those patients may benefit from emergent decompressive hemicraniotomy.15,16
Compared with the 13% death or dependence rate seen in the ISCVT cohort, our systematic review had 16% poor outcome or death despite good recanalization rates. In general, however, patients who underwent MT were in a worse clinical condition. For example, only 19% of patients in ISCVT were stuporous or comatose, compared with 47% in our series.
In 95% of patients in our series, complete or partial recanalization was achieved. Previous studies have shown that approximately two thirds of patients treated with anticoagulation also show recanalization, but in these patients, this process generally takes weeks or months.17 However, recanalization of the cortical veins cannot be achieved with MT because of the risk of perforation. Thrombosis of these veins is thought to be pivotal in the development of venous infarcts.18 With the invention of newer flexible devices, risk of venous sinus rupture and other catheter-related complications might be lower, although under-reporting of these complications is likely, because most included studies were retrospective and did not include consecutive cases.
What Is the Best Device for MT?
MT for CVT has evolved since its inception in 1996. In general, neurointerventionalists have preferred suction/aspiration devices. Dowd et al19 used AngioJet for the first time along with IST with good results. AngioJet is still one of the most frequently used devices.1 It has been used separately or in combination with balloon angioplasty. Because AngioJet is a bulky and stiff device, recanalization can be difficult, as is also suggested by our finding that only 55% of patients treated with AngioJet achieved complete recanalization. The use of AngioJet was also associated with a lower chance of good outcome and higher risk of complications, although these observations must be interpreted with caution because we had insufficient power to adjust for potential confounders. The Penumbra system is a more technically evolved device that has been used frequently in the past few years. The major advantages of Penumbra system over AngioJet are the smaller size and the bulk removal of a thrombus with suction without a need to completely withdraw the catheter. Choulakian et al20 reported the first use of Penumbra system for lysing CVT in 4 patients. All cases were treated with the Penumbra 0.41 which has a smaller lumen and simultaneous use of balloon angioplasty was required in 3 cases to augment thrombolysis. Good recanalization was obtained in all cases but only 3 of 4 patients had a good outcome. Our group reported the use of Penumbra 0.54, which has a bigger lumen that allows compatibility with other microcatheters, if additional therapies are required.12 The larger internal diameter of this catheter also allows for stronger thromboaspiration, potentially effecting more rapid sinus recanalization. The same catheter can be used for local tissue-type plasminogen activator infusion and thromboaspiration minimizing the use of recatheterization.
Other devices that have been used frequently are wire with microsnare or distal protection devices. Philips et al21 described the first use of wire in conjunction with microsnare for the treatment of CVT with good results. In 2012, Li et al10 published their case series of 52 patients in whom they used spiral shapeable wire along with Angioguard distal protection device (Cordis Inc) for MT while using Urokinase boluses and continuous infusion. They also used Autotransfusion System (Autolog, Medtronic, Inc) as a suction device. The new retrievable stents such as Solitaire have shown promising results, but because of limited sample size it is difficult to draw any conclusions.13 MERCI is the least favored device mainly because of its spiral component that often unravels during attempts at clot removal, and it is often harder to remove larger clots.1,20
Should MT Be Performed in Conjunction With IST?
Review of literature and our experience showed that most of the physicians preferred the use of MT with IST. Only less than one third of patients had undergone MT without IST. New or increased postprocedure intracranial hemorrhage was seen in 10% of all the 185 cases. Postprocedure hemorrhages happened in 7% of patients who underwent MT alone as compared with 11% of the patients who underwent MT with IST. This difference was not statistically significant, which may be the result of a small sample size. The risk of hemorrhagic complications should be an important end point in future studies that compare MT alone to MT with IST for the treatment of CVT, especially in the setting of preexisting hemorrhages.
What Are the Major Limitations of This Procedure?
Despite improvement in technique and devices, there are many limitations associated with the use of MT. The important ones are higher operating costs (devices, setup, etc), the difficulty of the procedure and access to procedure expertise. CVT is more prevalent in developing and underdeveloped countries where most of the population has limited access to healthcare resources.22,23
Certain complications are inherent to the use of these devices such as risk of vessel perforation. This complication was reported in only 1 patient, although under-reporting is probable as a result of a publication bias. The most important complication that can occur is a new ICH, which was reported in 10% of patients. This proportion is higher than what is generally reported in patients treated with anticoagulation, although only a small number of studies have examined this.1,24
Other complications that may occur are access site hematoma, soft tissue infections, iatrogenic arteriovenous fistula formation, and peripheral nerve injuries. All were rarely, or not at all, reported in any of the articles.
Limitations of the Study
Overall, the results of this study should be approached with caution, because its data are mainly based on retrospective case reports and case series. Clinicians and researchers alike tend to publish data with positive outcome more readily. A randomized control trial on endovascular treatment for patients with CVT is currently underway.25 Hopefully, this study will provide more solid data on the safety and efficacy of this procedure.
CVT is a disease with potential for high morbidity and mortality. Its natural history is well defined but not so is its treatment. Based on limited data, anticoagulation is the current standard of care, but more aggressive therapies, such as MT with or without IST, may be required in selected cases. Our systematic review suggests MT is reasonably safe in the majority of cases, but controlled studies are required to provide a definitive answer on the efficacy and safety of MT in patients with CVT.
Presented in part at the European Stroke Organization Conference, Glasgow, UK, April 17–19, 2015.
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.114.007465/-/DC1.
- Received September 16, 2014.
- Revision received January 5, 2015.
- Accepted January 7, 2015.
- © 2015 American Heart Association, Inc.
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