Frequency and temporal profile of recanalization after cerebral vein and sinus thrombosis

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1 ORIGINAL ARTICLE Frequency and temporal profile of recanalization after cerebral vein and sinus thrombosis C. Herweh a, M. Griebe b, C. Geisb usch c, K. Szabo b, E. Neumaier-Probst d, M. G. Hennerici b, M. Bendszus a, P. A. Ringleb c and S. Nagel c a Department of Neuroradiology, University of Heidelberg, Heidelberg; b Department of Neurology, Universit atsmedizin Mannheim, University of Heidelberg, Mannheim; c Department of Neurology, University of Heidelberg, Heidelberg; and d Department of Neuroradiology, Universit atsmedizin Mannheim, University of Heidelberg, Mannheim, Germany Keywords: anticoagulation, cerebral sinus and venous thrombosis, recanalization Received 7 August 2015 Accepted 1 October 2015 European Journal of Neurology 2015, 0: 1 7 doi: /ene Background and purpose: The temporal course of recanalization and its association with clinical outcome were analysed in our patients with cerebral sinus and/or venous thrombosis (CSVT) and follow-up magnetic resonance imaging (MRI). Methods: Between January 1998 and September 2014 all patients from our institutions with CSVT were systematically analysed. Baseline data, treatment characteristics and follow-up MRI were retrospectively recorded. The status of recanalization was assessed as complete (CRec), partial (PRec) or failed recanalization. Clinical follow-up was measured with the modified Rankin Scale. Excellent outcome was defined as modified Rankin Scale 0 1. Results: Ninety-nine patients were identified; 97% of these patients were treated with oral anticoagulation (OAC) and the median (min max) time of OAC was 7 months (1 84). CRec was achieved in 57.6% (57/99), PRec in 29.3% (29/99) and only 13 (13.1%) patients did not recanalize. The median (min max) time to PRec was 4 months ( ) and to CRec 6 months (2 34). Median time to last clinical follow-up was 8 months (1 88); 91.8% (89/99) had an excellent outcome at last clinical follow-up and only 2.1% (2/99) died. Only thrombosis of the superior sagittal sinus was independently associated with successful recanalization (odds ratio 16, 95% confidence interval 2 138). No severe haemorrhagic complications and no recurrence of CSVT occurred within clinical follow-up. No association of outcome and recanalization status was found. Conclusions: The recanalization rate of CSVT under OAC was high and the median time to CRec was 6 months. Thrombosis of the superior sagittal sinus is a positive predictor of recanalization. Outcome in this cohort was excellent but no significant association of outcome and recanalization status was found. EUROPEAN JOURNAL OF NEUROLOGY Introduction Currently the gold standard for diagnosis of cerebral sinus and/or venous thrombosis (CSVT) is cranial magnetic resonance imaging (cmri), including unenhanced images of the brain and the venous structures Correspondence: Simon Nagel, Department of Neurology, University Hospital Heidelberg, INF 400, Heidelberg, Germany (tel.: ; fax: ; simon.nagel@med.uni-heidelberg.de). to assess thrombus formation, oedema and haemorrhage, as well as venous MR angiography (MRA) to assess vessel patency [1,2]. Contrast-enhanced techniques are considered to be more sensitive than flow-dependent ones [3]. MRA is also a suitable tool to assess recanalization of veins and sinuses in the temporal course of the disease. A limited number of previous studies have assessed the temporal profiles of recanalization after CVST [4 10]. Importantly, most of these cohort studies had a limited number of 1

2 2 C. HERWEH ET AL. patients and the results regarding the frequency and temporal profile of recanalization showed substantial variation. No recanalization was reported in 0% 29% and the rate of complete recanalization ranged from 30% to 66% of patients, whereas the rest showed at least partial recanalization [4,6 8,10]. The two largest of the aforementioned studies (n = 91 and n = 102 patients) showed conflicting results regarding the association of recanalization with clinical outcome [4,6]. The data of 99 patients with CVST who were treated in the Department of Neurology in Heidelberg or Mannheim of the University of Heidelberg and who had at least one clinical and one radiological follow-up examination were analysed. The site of the initial thrombosis and its extent of recanalization were assessed; our aim was to describe parameters significantly associated with the state of recanalization as well as the association of recanalization with longterm outcome. Methods Our medical records were systematically searched for patients who were treated for CVST in our institutions (University of Heidelberg, Department of Neurology in Heidelberg and Mannheim) between January 1998 and September 2014 and for whom clinical and radiological follow-up data were available until January Patients with septic or traumatic CVST, as well as patients undergoing endovascular recanalization therapy, were excluded. All relevant clinical data were retrospectively recorded and clinical severity was measured by using the modified Rankin Scale (mrs) at admission, discharge and clinical follow-up visits. Either computed tomography (CT) (Somatom Volume Zoom) or venous MRA (venous time-of-flight or contrast enhanced) at a 1.5-T scanner (Symphony, Sonata, Avanto) or a 3-T scanner (Trio, Skyra; all scanners from Siemens Medical, Erlangen, Germany) [3] was performed to establish the diagnosis in all patients. When MRI was performed diffusion-weighted imaging, T2-weighted imaging, T1-weighted imaging before and after application of contrast agent and susceptibility-weighted imaging were also analysed if available in order to assess the site and extent of thrombosis and parenchymal abnormalities such as cerebral oedema, infarction and haemorrhage. The dominant side of the transverse/sigmoid sinus was semi-quantitatively defined as the vessel with 50% or more in transverse diameter compared to the contralateral side. The vessel diameter was determined on sectional T1- or T2-weighted images or, if CT scans were available, it was determined according to the bony sulcus of the sigmoid sinus. Follow-up MRI (FuMRI) was not performed according to a strictly timed protocol during follow-up, but at least one scan within 6 months was recommended in every patient. Vessel recanalization was retrospectively assessed as overall partial (PRec) or complete (CRec) according to Stolz et al. [10] by four investigators on a consensus basis (CH, KS, MG and SN). If recanalization was observed, the point in time of this MRI was used as the moment of recanalization. Excellent outcome was defined as mrs 0 1, although it was appreciated that for less affected monosymptomatic or oligosymptomatic CVST patients the mrs might not be the most adequate severity measuring instrument. Major haemorrhage during follow-up was defined as intracranial haemorrhage or any other haemorrhage requiring hospitalization or transfusion. All patients were initially treated in accordance with in-house treatment protocols (regarding anticoagulation and symptomatic treatment) on the general neurological ward, the stroke unit or the neurointensive care unit. In all patients initial anticoagulation was commenced by either intravenous unfractionated heparin (target partial thromboplastin time s) or body-weight-adjusted low molecular weight heparin (LMWH) and thereafter oral anticoagulation (OAC) was started by the choice of the treating physician with either the standard treatment phenprocoumon [vitamin K antagonist (VKA), target international normalized ratio 2 3] or non-vitamin-k-antagonist oral anticoagulants (NOACs). Since 2013 NOACs have increasingly been used by us without a strict protocol and on the basis of individual decisions of the treating physician and the patient since they can still be regarded as off-label therapy [11]. All data were analysed with SPSS (Version 21.0; IBM Corp., Armonk, NY, USA). Frequencies were determined for categorical variables; for ordinal and metric data the median was calculated, together with the minimal and maximal values. For determination of predictors for recanalization and outcome odds ratios with a 95% confidence interval were calculated in a multivariate analysis. A P value of <0.05 was considered to be significant. The local ethics committee approved the study (S-502/2012). Results A total of 99 patients were included in the study. The median age was 38 years (range 17 80) and the majority of patients were female (81.8%). The baseline clinical parameters are summarized in Table 1. The most common risk factor was oral contraception in 38

3 RECANALISATION AFTER CEREBRAL VENOUS THROMBOSIS 3 of 81 women (46.9%), followed by smoking in 26.3% of patients. The most common clinical symptom was headache in 76.8% of patients and in 30 of these 76 patients (39.5%) headache was the only clinical symptom at presentation. The median mrs on admission was 1 (0 5) and the median time from symptom onset to presentation was 4 days (0 50). In the majority of patients (88.9%) the diagnosis of CVST was established with MRI and MRA. The site and extent of the thrombosis together with parenchymal abnormalities on baseline imaging are also displayed in Table 1. The most abundantly occluded vessels were the transverse/sigmoid sinus (74.7%). The majority of patients (57.8%) had a lateralized developed transverse and sigmoid sinus and in 14 (38.9%) of the patients the dominant side was affected compared to 22 (61.1%) patients with thrombosis in the non-dominant vessel. The superior sagittal sinus showed signs of thrombosis in 48.5% and the jugular vein in 43.4% of patients, respectively. In 63.3% of patients more than one sinus/vein was affected and in eight patients (8.1%) the CVST was bilateral. Intracerebral haemorrhage occurred in 29 patients (29.3%) and 33 Table 1 Baseline clinical and radiological parameters Baseline variables, N = 99 Value Age (years), median, min max 38, Gender (female), n (%) 81 (80.2) Clinical syndrome Headache, n (%) 76 (76.8) Isolated headache, n (%) 30 (30.3) Paresis, n (%) 23 (23.2) Speech impairment, n (%) 21 (20.8) Epileptic seizure, n (%) 37 (37.4) Visual symptoms, n (%) 22 (22.2) Time from onset to admission 4, 0 50 (days), median, min max Clinical risk factors Oral contraception, n/n (%) 38/81 (46.9) Other hormonal therapy, n (%) 7 (7.1) Steroid therapy, n (%) 12 (12.1) Smoking, n (%) 26 (26.3) Pregnancy/puerperium, n/n (%) 5/81 (6.2) Thrombophilia, n (%) 15 (15.2) Malignancy, n (%) 4 (4) Previous thromboembolic event, n (%) 12 (12.1) Imaging brain lesion Haemorrhage, n (%) 29 (29.3) Oedema/infarction, n (%) 33 (33.3) Imaging vessel Superior sagittal sinus, n (%) 48 (48.5) Transverse/sigmoid sinus, n (%) 74 (74.3) Deep veins (rectus, inferior sagittal), n (%) 12 (12.1) Jugular vein, n (%) 43 (43.4) Cortical veins, n (%) 22 (22.2) Bilateral thrombosis, n (%) 8 (8.1) Thrombosis in more than one vessel, n (%) 63 (63.6) patients (33.3%) suffered from oedema or venous infarction. One patient with a malignancy and thrombocytopaenia suffered from a new intracerebral haemorrhage under anticoagulation with LMWH during hospital stay. Details of treatment and follow-up are summarized in Table 2. Ninety-five patients (97%) received OAC with a median duration of 7 months (1 84) and nine patients acquired a lifelong indication for OAC due to underlying thrombophilia. Three patients were only treated with LMWH due to underlying malignancy or because the CVST was only mild ; treatment duration with LMWH ranged between 6 and 10 months. Thirteen patients (13.1%) were treated with a NOAC and the rest with VKA. Two patients suffered from epistaxis, two women from increased menstruation and one patient reported transient petechial haemorrhage. No major bleeding events and no recurrent CVST were recorded during follow-up. All patients had at least one follow-up imaging and only in one patient was this done with CT/CT angiography. The median number of FuMRI was 1 (1 5) with a range between 1 week and 53 months after CVST (median time to first FuMRI was 6 months and to last FuMRI was 7 months) and 48.5% of patients had more than one FuMRI. Median time to last clinical follow-up was 8 months (1 88) and excellent outcome (mrs 0 1) was achieved in 89 patients (91.8%). 57.6% of patients achieved CRec; of these 64.9% (37 of 57) Table 2 Treatment and follow-up parameters Treatment, N = 99 Value Duration of hospital stay (days), median, min max 9, 2 30 Oral anticoagulation (OAC), n (%) 96 (97) Duration of OAC (months), median, min max 7, 1 84 Direct anticoagulant, n (%) 13 (13.1) Hemicraniectomy, n (%) 2 (2) Hypothermia, n (%) 1 (1) Modified Rankin Scale (mrs) at discharge, 1, 0 5 median, min max Excellent outcome at discharge (mrs 0 1), n (%) 82 (82.8) Follow-up Time of last clinical follow-up (months), median, 8, 1 88 min max RS at follow-up, median, min max 0, 0 6 Excellent outcome at follow-up (mrs 0 1), 89 (91.8) n (%) Minor haemorrhagic complications, n (%) 5 (5.5) Follow-up imaging Complete recanalization (CRec), n (%) 57 (57.6) Partial recanalization (PRec), n (%) 29 (29.3) No recanalization, n (%) 13 (13.1) Complete recanalization at first MRI, n/n (%) 37/57 (64.9) Time to PRec (months), median, min max 4, Time to CRec (months), median, min max 6, 2 34

4 4 C. HERWEH ET AL. were completely recanalized at first FuMRI. 29.3% showed PRec and only 13.1% did not recanalize during follow-up. Median time to PRec was 4 months ( ) and median time to CRec was 6 months (2 34). A detailed outline of FuMRIs as well as of (cumulative) recanalization rates grouped into time intervals is displayed in Table 3. Of note, the patient with the longest time to CRec (34 months) only had one FuMRI and therefore it is unclear at what time the vessel recanalized. Only one of the clinical baseline variables showed significant correlation with recanalization (Table 4): women after their menopause undergoing hormonal replacement therapy or women under hormonal treatment for in vitro fertilization at the time of thrombosis showed significantly impaired recanalization during follow-up (P = 0.046). Notably, any hormonal therapy was discontinued after diagnosis of CVST. The use of NOAC as the anticoagulant drug was not associated with recanalization (P = 0.68). Excellent clinical outcome on follow-up was also not associated with the state of recanalization (P = 0.59). However, one site of vessel occlusion showed a significant association with recanalization, i.e. thrombosis of the superior sagittal sinus (P = 0.001, Table 4 and Fig. 1). In a multivariate analysis with adjustment for age and hormonal therapy as covariates only thrombosis of the superior sagittal sinus remained to be a positive predictor of successful (partial and complete) recanalization [odds ratio (OR) 16, 95% confidence interval (CI) 2 138]. Discussion Here clinical and radiological outcome measures are reported of a large cohort of patients with CVST from both neurological departments of the University of Heidelberg whose data have been collected over a period of 16 years. The most abundant vessel thrombosis was that of the transverse and sigmoid sinus but only thrombosis of the sagittal superior sinus was significantly associated with successful recanalization (OR = 16, 95% CI 2 138) after multivariate analysis. The majority of patients showed partial or complete recanalization and in only 13.1% were no signs of recanalization present over time. The time course of recanalization was dependent on the scheduled FuMRI, but it was generally early since 96% of patients showed at least partial recanalization (median 4 months) and almost 90% achieved complete recanalization (median 6 months) within the first year after the onset. Importantly, no significant correlation of the status of recanalization with long-term outcome was found after multivariate analysis. Baseline clinical and underlying risk factors and gender distribution were similar in our cohort compared to the relevant published data [4,6,12]. Overall outcome at last follow-up (median 8 months) of our patients was excellent (mrs 0 1) in 91.8%, which is similar to the two larger previously published MRI follow-up studies [4,6] and better than in the International Study on Cerebral Vein and Dural Sinus Thrombosis [12], which is at least partly explained by a selection bias. It was shown previously that both the severity of the initial clinical syndrome (mrs on admission) and the presence of intracerebral haemorrhage were negative predictors of clinical outcome in our patients [13]. In this analysis our focus was on the time course and extent of recanalization and its association with clinical outcome after CVST. All previous studies indicated that the majority of patients showed at least signs of partial recanalization over time and a meta-analysis combining 154 patients showed that recanalization rates were not different at 3 and at 12 months after onset (84% vs. 85%) [14]. In one previous study with 91 patients, recanalization up to 6 months was also high (47% complete and 37% partial) but no assessment of the temporal evolution was reported [15]. Arauz et al. [4], however, presented for the first time cumulative recanalization rates over time which were very similar to our results. They found an obvious increase of patients with complete Table 3 Detailed outline of number of patients with points in time of first follow-up MRI, last follow-up MRI as well as the earliest moment of any recanalization (PRec or CRec, whichever was first) and complete recanalization, grouped in 3-month periods Time period First follow-up MRI, all patients, N (%, cumulative %) Last follow-up MRI all patients, N (%, cumulative %) Earliest proof of any recanalization, N = 86, N (%, cumulative %) Earliest proof of complete recanalization, N = 57, N (%, cumulative %) 0 3 months 34 (34.3, 34.3) 9 (9.1, 9.1) 24 (27.9, 27.9) 8 (8.1, 14) >3 6 months 43 (43.5, 77.8) 34 (34.3, 43.4) 41 (47.7, 75.6) 28 (49.1, 63.1) >6 9 months 14 (14.1, 91.9) 17 (17.2, 60.6) 15 (17.4, 93) 9 (15.8, 78.9) >9 12 months 2 (2, 93.9) 11 (11.1, 71.7) 2 (2.3, 95.3) 7 (12.3, 92.2) After 12 months 6 (6.1, 100) 28 (28.3, 100) 4 (4.7, 100) 5 (8.8, 100)

5 RECANALISATION AFTER CEREBRAL VENOUS THROMBOSIS 5 Table 4 Univariate analysis of factors associated with recanalization Variables No recanalization, n = 13 (%) Partial/complete recanalization, n = 86 (%) P value Demographics and risk factors Gender female 11 (84.6) 70 (81.4) 1.0 Age in years (median, min max) a 44, , Oral contraception 5/11 (45.5) 33/70 (47.1) 1.0 Smoking 3 (23.1) 23 (26.7) 1.0 Pregnancy/puerperium 0 (0) 5/70 (7.1) 1.0 Steroids 1 (7.7) 11 (12.8) 1.0 Hormones 3 (23.1) 4 (4.6) Thrombophilia 2 (15.4) 13 (15.1) 1.0 Malignancy 0 (0) 4 (4.7) 1.0 Clinical syndrome Headache 8 (61.5) 68 (79.1) 0.17 Seizures 2 (15.4) 35 (40.7) 0.12 Paresis 2 (15.4) 21 (24.4) 0.73 Aphasia 4 (30.8) 17 (19.8) 0.46 Visual symptoms 2 (15.4) 20 (23.3) 0.73 Affected vessel Transverse/sigmoid sinus 12 (92.3) 62 (72.1) 0.18 Dominant transverse/sigmoid sinus 2/7 (28.6) 12/29 (41.4) 0.68 Superior sagittal sinus 1 (7.7) 47 (54.7) Deep veins, including inferior 1 (7.7) 11 (12.8) 1.0 sagittal sinus and straight sinus Cortical veins 2 (15.4) 20 (23.3) 0.73 Jugular vein 7 (53.8) 36 (41.9) 0.55 Bilateral thrombosis 0 (0) 8 (9.3) 0.59 Thrombosis of more than one vessel 7 (53.8) 56 (65.1) 0.53 Brain lesion Haemorrhage 5 (38.5) 24 (27.9) 0.51 Oedema/infarction 3 (23.1) 30 (34.9) 0.53 Time from onset to admission in days (median, min max) a 3.5, , mrs at follow-up (median, min max) a 0, 0 1 0, Excellent outcome at follow-up 13 (100) 78 (90.7) 0.59 Excellent outcome at follow-up (subgroup of patients with 3/3 (100) 20/25 (80) 0.54 mrs 3 on admission) Duration of OAC in months (median, min max) a 7, , NOAC therapy 2 (15.4) 11 (12.8) 0.68 Chi-squared test. mrs, modified Rankin Scale; OAC, oral anticoagulation; NOAC, non-vitamin-k-antagonist oral anticoagulant. a Mann Whitney test. Bold P values indicate significance. (a) (b) (c) Figure 1 Sequential and differential recanalization of a complex CSVT. Maximum-intensity projection images of contrast-enhanced venous MRA at day 2 (a), day 7 (b) and after 7 months (c) from a 21-year-old female patient. The initial image (a) shows extensive thrombosis of the superior sagittal and right transverse sinus (SSS and rst, respectively). After 5 days (b), there is partial recanalization of the SSS but not the rst. At long-term follow-up (c) there is complete recanalization of the SSS and partial recanalization of the rst.

6 6 C. HERWEH ET AL. recanalization from 3 to 12 months (i.e. 32.4% to 72.9%) and concluded that in contrast to previous studies recanalization is a dynamic process up to 1 year after the disease. Presently, a striking increase of patients with complete recanalization from 3 months (13.8%) up to 12 months (89.7%) was also found, which supports this finding. Only seven of our patients were documented who recanalized between 12 and 18 months (in two cases this was the only MRI) and only one patient who presented with complete recanalization after 34 months; however, this was the only FuMRI as well. Therefore no conclusion on the temporal evolution can be made in these patients. Overall, our data support the statement that recanalization after CVST usually occurs within the first 3 6 months but can develop up to 12 months and in rare occasions even thereafter. The assessment of the MRI should carefully consider potential differences in imaging parameters over time and artefacts that might lead to misinterpretation of recanalization. In our opinion the decision whether to continue OAC after 12 months should not be based on the status of recanalization but on the risk of recurrent thrombosis and underlying thrombophilia. Conflicting results were reported with regard to the association of recanalization and outcomes by Putaala et al. [6] and Arauz et al. [4]. Despite a significant univariate association, recanalization was not associated with outcome after multivariate analysis in the study by Putaala et al. whilst Arauz et al. showed that patients with complete recanalization had a greater chance of good functional outcome (hazard ratio 5.17, 95% CI ) in an adjusted Cox proportionalhazards model for covariates. Here, no significant association of recanalization and outcome was found and also no association of recanalization and age was found, even when the cohort was divided at age 37 and 50 as previously described [4,6]. Hence, in contrast to stroke patients with larger artery occlusions, where the association of recanalization with outcome is evident and strong, this association in CVST patients seems to be less distinct. An independent association with a positive prediction of recanalization was only found in our patients with an occluded superior sagittal sinus (OR = 16, 95% CI 2 138). This occlusion type also showed a higher percentage of complete recanalization in the Mexican study, thereby confirming our results [4]. The majority of our patients (57.8%) had a dominant transverse and sigmoid sinus, but it could not be demonstrated that thrombosis of either the dominant or non-dominant side is related to recanalization or long-term outcome (Table 4). A strong trend, however, was found with regard to outcome on discharge, i.e. patients with thrombosis of the dominant side were more likely to be dependent (21.4% vs. 0%, P = 0.051). According to our present work and previously published data [11] NOACs appear to be similar effective anticoagulatory drugs compared to VKAs in CVST. Although only 13 patients in total were treated with a NOAC (Table 4), to our knowledge this is so far the largest published cohort. No major haemorrhagic complications occurred under either treatment. It also appears that the time point of treatment initiation with heparins after the onset does not have an impact on the effectiveness of recanalization (Table 4). The significance of our results is of course hampered by the retrospective design. Moreover, different scanners were used and the time points of FuMRIs were not similar for every patient but were planned individually by the treating physicians; therefore the determination of the time course and extent of recanalization is impaired. Nonetheless, this is the second largest cohort of CVST patients with multiple FuMRIs and clinical follow-up. Sounder data can only be generated through larger prospective registries or randomized trials. In summary, it has been shown that recanalization after CVST is a dynamic process that, in the majority of patients, occurs within 3 6 months, in fewer patients within 6 12 months and only in rare cases thereafter. A significant association of recanalization with clinical outcome was not found, but thrombosis of the superior sagittal sinus was a strong positive predictor of successful recanalization. There was no funding. Acknowledgement Disclosure of conflicts of interest S. Nagel and P. Ringleb have received travel expenses and lecture honoraria from Bayer Healthcare. References 1. Bousser MG. Cerebral venous thrombosis: diagnosis and management. J Neurol 2000; 247: Bonneville F. Imaging of cerebral venous thrombosis. Diagn Interv Imaging 2014; 95: Lettau M, Laible M, Barrows RJ, Heiland S, Bendszus M, Hahnel S. 3-T contrast-enhanced MR angiography with parallel imaging in cerebral venous and sinus thrombosis. J Neuroradiol 2011; 38: Arauz A, Vargas-Gonzalez JC, Arguelles-Morales N, et al. Time to recanalisation in patients with cerebral venous thrombosis under anticoagulation therapy. J Neurol Neurosurg Psychiatry [Epub ahead of print].

7 RECANALISATION AFTER CEREBRAL VENOUS THROMBOSIS 7 5. Baumgartner RW, Studer A, Arnold M, Georgiadis D. Recanalisation of cerebral venous thrombosis. J Neurol Neurosurg Psychiatry 2003; 74: Putaala J, Hiltunen S, Salonen O, Kaste M, Tatlisumak T. Recanalisation and its correlation to outcome after cerebral venous thrombosis. J Neurol Sci 2010; 292: Rottger C, Trittmacher S, Gerriets T, Blaes F, Kaps M, Stolz E. Reversible MR imaging abnormalities following cerebral venous thrombosis. AJNR Am J Neuroradiol 2005; 26: Schultz DW, Davis SM, Tress BM, Kilpatrick CJ, King JO. Recanalisation and outcome cerebral venous thrombosis. J Clin Neurosci 1996; 3: Strupp M, Covi M, Seelos K, Dichgans M, Brandt T. Cerebral venous thrombosis: correlation between recanalisation and clinical outcome a long-term follow-up of 40 patients. J Neurol 2002; 249: Stolz E, Trittmacher S, Rahimi A, et al. Influence of recanalisation on outcome in dural sinus thrombosis: a prospective study. Stroke 2004; 35: Geisbusch C, Richter D, Herweh C, Ringleb PA, Nagel S. Novel factor xa inhibitor for the treatment of cerebral venous and sinus thrombosis: first experience in 7 patients. Stroke 2014; 45: Ferro JM, Canhao P, Stam J, Bousser MG, Barinagarrementeria F. Prognosis of cerebral vein and dural sinus thrombosis: results of the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT). Stroke 2004; 35: Geisbusch C, Lichy C, Richter D, Herweh C, Hacke W, Nagel S. Clinical course of cerebral sinus venous thrombosis. Data from a monocentric cohort study over 15 years. Nervenarzt 2014; 85: Dentali F, Gianni M, Crowther MA, Ageno W. Natural history of cerebral vein thrombosis: a systematic review. Blood 2006; 108: Putaala J, Hiltunen S, Salonen O, Kaste M, Tatlisumak T. Recanalization and its correlation to outcome after cerebral venous thrombosis. J Neurol Sci 2010; 292:

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