Venous Thrombotic Recurrence After Cerebral

Venous Thrombosis
A Long-Term Follow-Up Study
Paola Palazzo, MD, PhD*; Pierre Agius, MD*; Pierre Ingrand, MD; Jonathan Ciron, MD;
Matthias Lamy, MD; Aline Berthomet, MD; Paul Cantagrel, MS; Jean-Philippe Neau, MD

Background and Purpose—After cerebral venous thrombosis (CVT), the risk of venous thrombotic events was estimated at
2% to 3% for a new CVT and 3% to 8% for extracranial events. However, because of the paucity of prospective studies,
the clinical course of CVT is still largely unknown. We aimed to prospectively evaluate the rate of thrombosis recurrence
in a cohort of CVT patients with a long-term follow-up and to detect predisposing factors for recurrence.
Methods—Consecutive CVT patients with complete clinical, radiological, biological, and genetic data were systematically
followed up. New venous thrombotic events were detected after hospital readmission and imaging confirmation.
Results—One-hundred eighty-seven patients (mean age 45±18 years, 67% women) with angiographically confirmed CVT
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were included. Cause was found in 73% of patients. Coagulation abnormality and JAK2 gene mutation were detected
in 20% and 9%, respectively. Median follow-up length was 73 months (range 1–247 months). Mean duration of the
oral anticoagulant treatment was 14 months. Mortality rate was 2.5% per year, with 2% in-hospital mortality. During
follow-up, CVT reoccurred in 6 patients, whereas 19 subjects had a symptomatic extracranial venous thrombotic event,
with cumulative venous thrombotic recurrence rates of 3% at 1 year, 8% at 2 years, 12% at 5 years, and 18% at 10
years. A previous venous thrombotic event (hazard ratio, 2.8; P=0.018), presence of cancer or malignant hemopathies
(hazard ratio, 3.2; P=0.039), and unknown CVT causes (hazard ratio, 2.81; P=0.024) were independently associated with
recurrence.
Conclusions—In our cohort of CVT patients followed on average for >6 years, subjects with a previous venous thrombotic
event, cancer/malignant hemopathies, and unknown CVT causes were found to be at higher risk of recurrence. 
(Stroke. 2017;48:321-326. DOI: 10.1161/STROKEAHA.116.015294.)
Key Words: female ◼ mutation ◼ risk ◼ thrombophilia ◼ venous thromboembolism

C erebral venous thrombosis (CVT) is an uncommon dis-

ease that mainly affects subjects younger than 40 years of
age, patients with thrombophilia, and women who are pregnant
or receiving hormonal contraceptives. The annual incidence is
estimated to be 3 to 4 cases per million,1 which increases to
12 cases per 100 000 deliveries during the peripartum period.2
Mortality and recurrence rates are lower when compared
with arterial stroke, with an estimated annual risk of new
venous thrombotic events after a first CVT at 2% to 3% for a
new CVT and 3% to 8% for extracranial events.3–5
However, because of a paucity of prospective studies with
long-term follow-up, recurrence of venous thrombosis (VT)
after CVT is still largely unknown, as are predisposing fac-
tors for recurrence. In fact, mixed results exist on the factors
associated with recurrence risk. In a multicenter observa-
tional study of 624 adult patients with CVT, male sex and
polycythemia/thrombocythemia were found to be the only
independent predictors of venous thromboembolism after
CVT.6 These results were not confirmed by other authors who
observed an association between recurrence and a history of
previous extracerebral venous thrombotic events,7 whereas in
another study no variable was found to be significantly associ-
ated with recurrent VT.4 No study to date has estimated risk of
VT recurrence with different CVT causes.
We, therefore, aimed to prospectively evaluate the incidence
of recurrent cerebral and extracerebral venous thrombotic
events in a cohort of CVT patients and to detect clinical, bio-
logical, and radiological factors associated with VT recurrence.
Methods
A database was established to prospectively follow up a cohort of con-
secutive patients with a first episode of angiographically proven CVT

Received September 2, 2016; final revision received November 3, 2016; accepted November 10, 2016.
From the Department of Neurology, Poitiers University Hospital and University of Poitiers, France (P.P., P.A., J.C., M.L., A.B., P.C., J.-P.N.); Department
of Neurology, S. Giovanni Calibita-Fatebenefratelli Hospital, Rome, Italy (P.P.); and Clinical Investigation Center INSERM CIC-P 802, Poitiers University
Hospital, France (P.I.).
*Drs Palazzo and Agius contributed equally.
Correspondence to Paola Palazzo, MD, PhD, Department of Neurology, Poitiers University Hospital, 2 rue de la Milétrie, 86021 Poitiers, France. E-mail
paola.palazzo@chu-poitiers.fr; ppalazzo@hotmail.it
© 2016 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.116.015294

321
 322  Stroke  February 2017
admitted to primary (n=3) and comprehensive (n=1) stroke centers
in the French Poitou-Charentes region (1.8 million inhabitants, mean
age 42 years, 48% <40-year old, 51% women) from January 2005 to
December 2014. The study was approved by the local ethics commit-
tee, and all enrolled subjects signed informed consent forms. Clinical
diagnosis of CVT was confirmed by brain computed tomography
(CT) with CT venography, magnetic resonance imaging combined
with magnetic resonance venography, conventional angiography, or
multimodal imaging. Complete clinical, radiological, biological, and
genetic data were collected, including demographic data, symptoms
and signs from onset to diagnosis, Glasgow Coma Scale and National
Institutes of Health Stroke Scale scores in the acute phase, thrombus
localization, and presence of parenchymal lesions. Thrombophilic
screening was assessed in all the study subjects, including factor V
Leiden, G20210A mutations, lupus anticoagulant, and anticardiolipin
antibodies. However, proteins C and S and antithrombin III were
not systematically assessed before anticoagulation was started and
not controlled after treatment interruption; therefore, they were not
analyzed in this study. Patients underwent lumbar puncture unless
contraindicated. The JAK2 V617F mutation analysis was systemati-
cally assessed in all subjects included from 2008 using a real-time
polymerase chain reaction method.
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Follow-up visits were performed at 6 months, including neuro-
imaging follow-up, at 12 months, and yearly thereafter at outpa-
tient evaluation that included neurological examination. If in-person
evaluation was impossible, alternative methods included a telephone
interview of the patient or an interview with a relative or general
practitioner. Subjects known to be hospitalized for any reason during
follow-up underwent direct inpatient neurological evaluation.
Follow-up data recorded included: disability (modified Rankin
Scale), death, recurrent symptomatic CVT (new symptoms with
new thrombosis on repeated neuroimaging), and other symptomatic
venous thrombotic events.
Primary outcome was cerebral or extracranial VT recurrence. All
the new venous thrombotic events were detected after readmission
to regional hospitals and received imaging confirmation. In case of
multiple recurrences, only the first one was included in the time-to-
event analysis.
Clinically suspected deep vein thrombosis (DVT) was confirmed by
duplex ultrasonography, CT, or magnetic resonance imaging venog-
raphy. Symptomatic pulmonary embolism (PE) was confirmed by
contrast-enhanced CT or ventilation–perfusion lung scan interpreted
as high probability for PE. Symptomatic portal vein thrombosis was
confirmed by contrast-enhanced CT or duplex ultrasonography. A
recurrent CVT was distinguished from the original thrombosis by
comparing serial imaging. To be classified as a recurrent CVT, new
or recurrent symptoms had to develop with new filling defects in the
follow-up study not present in the first images or in an interval study
showing thrombus resolution.
Statistical Analyses
The Kaplan–Meier product-limit method was used to calculate cumu-
lative recurrence rates and SE. Cox proportional hazards models were
used for univariate and multivariate prognostic analyses. All variables
with a P value <0.2 at univariate analysis were entered in the multi-
variate analysis. The final model was obtained after applying a back-
ward elimination procedure; all variables with a P value <0.05 were
retained. All analyses were performed with SAS release 9.3 software.
Results
One-hundred ninety-four patients with confirmed CVT were
enrolled in our prospective observational study. Seven (3.6%)
patients were lost to follow-up after discharge and excluded
from the study. Of the remaining 187 patients (mean age 45±18
years, 67% women, 97% white), 98% had an admission Glasgow
Coma Scale score between 9 and 15, and 2% were comatose
(Glasgow Coma Scale score of <9). Sixty-two patients (33%)
presented with isolated intracranial hypertension. Lumbar
puncture was performed in 99 patients: 20 patients had >5
cells and 47 had >45 mg/dL protein. Demographic, clinical,
and imaging features are shown in Table 1.
CVT cause was found in 73% of subjects (Table 2). Genetic
or acquired thrombophilia was detected in 20% of subjects,
mainly represented by factor V or II mutation. JAK2 gene
analysis was assessed in 120 patients, and a mutation was
detected in 9% (n=11) of them. A pharmacological cause was
observed in 47% of patients, mainly (91%) represented by
hormonal contraceptives or replacement therapy and less fre-
quently by chemotherapy.
In the acute phase, 185 (99%) patients were anticoagulated
with intravenous heparin (94%) or subcutaneous low-molec-
ular–weight heparin (6%) in therapeutic dosages followed by
oral vitamin K antagonists with a target international normal-
ized ratio of 2:3.8 One patient was treated with local endovascu-
lar thrombolysis, and 1 underwent mechanical thrombectomy.
Jugular vein stenting was performed in 2 patients, and 1 had
optic nerve fenestration. Additional treatment included anti-
epileptic medication (59 patients [32%]), mannitol (13 [7%]),
and acetazolamide (22 [12%]).
Mean and median follow-up lengths were 80 (SD 60)
and 73 months (range 1–247 months), respectively. Patients
received oral anticoagulant treatment for 14 months on aver-
age. Mortality rate was 2.5% per year with 2% in-hospital
mortality and 17% overall mortality, mainly related to can-
cer or hematologic malignancies. Discharge modified Rankin
Scale score was 0 to 1 in 74% of patients, whereas 8% of them
had a slight residual disability (modified Rankin Scale score
of 2) and 16% moderate to severe disability (modified Rankin
Scale score of 3–5).
During follow-up, 30 new venous thrombotic events
occurred in 25 CVT patients. CVT reoccurred in 6 patients,
whereas 19 subjects had new extracranial venous thrombotic
events, represented by DVT (12 patients), PE (5 patients),
and portal vein thrombosis (2 patients). A single new event
occurred in 23 patients, whereas 1 patient experienced CVT
followed by PE, and 1 had 5 episodes of DVT. The first recur-
rent event was included in the analysis.
The cumulative venous thrombotic recurrence rate was
3±1% at 1 year, 8±2% at 2 years, 12±3% at 5 years, and
18±4% at 10 years. Recurrence rate is represented in Figure.
In patients with a new CVT, mean recurrence delay was 28.5
months (SD 19.7).
In 1 of the 6 patients with a recurrent CVT and 1 of the
19 patients with a new extracranial venous thrombotic event
(PE), mortality was directly attributable to the recurrence.
In univariate analysis, recurrence was associated with older
age, a previous venous thrombotic event, absence of hormonal
agents, presence of cancer or malignant hemopathy, and
unknown causes (Table 3). In addition, patients who discon-
tinued estrogens after CVT displayed decreased recurrence
rates compared with subjects who had not taken hormonal
treatment (P=0.0036).
No association was found between the duration of antico-
agulation treatment and the recurrence risk in the overall study
population (P=0.70) or the subgroup of patients with CVT of
undetermined cause (P=0.30).
 Palazzo et al   Venous Thrombotic Recurrence After CVT    323

Table 1.  Demographic, Clinical, Biological, and Radiological Table 1.  Continued
Characteristics of the Study Cohort
n=187
n=187
 Any parenchymal lesion 78 (42)
Age at first CVT, mean (SD), y 45 (18)
  
Ischemic lesions 72 (39)
Female sex 126 (67)   
Hemorrhagic lesions 60 (32)
BMI, mean (SD) 25 (7)   
Edema 56 (30)
Current smoking 54 (29) Laboratory exams
Diabetes mellitus 7 (4)  Hemoglobin, g/dL, mean, (SD) 13.4 (2)
Previous stroke 4 (2)  Platelets, giga/L, mean, (SD) 266 (109)
CAD 7 (4) Thrombophilia testing
Dyslipidemia 28 (15)  Factor V mutation‡ 14 (8)
Arterial hypertension 42 (22)  Factor II mutation§ 18 (11)
Hyperhomocysteinemia* 26 (28)  JAK2 mutation‖ 11 (9)
Previous VTE 24 (13)  Anti-β2-GP1 antibodies 1 (0.6)
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Family history of VTE 38 (20)  Anticardiolipin antibodies 4 (2)

History of miscarriages† 19 (15) Data are expressed as n(%) unless specified. BMI indicates body mass index;
CAD, coronary artery disease; CVT, cerebral venous thrombosis; GCS, Glasgow
Clinical presentation Coma Scale; NIHSS, National Institutes of Health Stroke Scale; and VTE, venous
 Asymptomatic 3 (2) thrombotic events.
*Homocysteine was tested in 94 subjects (50%); percentage was calculated
 Altered mental status 17 (9) in this subgroup.
 Headache 167 (89) †Percentage calculated in the female subgroup.
‡Evaluated in 173 subjects (93%); percentage was calculated in this subgroup.
 Focal deficits 66 (35) §Evaluated in 167 subjects (89%); percentage was calculated in this subgroup.
 Intracranial hypertension 102 (55) ‖Evaluated in 120 subjects (64%); percentage was calculated in this subgroup.

 Seizures 55 (29)
When all potential risk variables with P value <0.2 at uni-
 GCS score, mean (SD) 14.6 (0.3) variate analysis were entered into multivariate model, a previ-
 NIHSS score, mean (SD) 3.5 (0.5) ous venous thrombotic event (hazard ratio [HR], 2.8; P=0.018),
presence of cancer or malignant hemopathy (HR, 3.2; P=0.039),
 Clinical onset delay
and unknown CVT cause (HR, 2.81; P=0.024) were indepen-
≤7 d
   111 (59) dently associated with any first VT recurrence (Table 3).
  
7–21 d 45 (24)
Table 2.  Cerebral Venous Thrombosis Causes in the Study
≥21 d
   31 (17) Population
Neuroimaging
n=187
 Occluded sinus number, mean (SD) 2.4 (2.4)
Cryptogenic 51 (27)
 Site of thrombosis
Recent trauma 9 (5)
  Superior sagittal sinus 94 (50)
CNS infection 29 (16)
  Inferior sagittal sinus 12 (6) Chronic inflammatory disease 9 (5)
  Right lateral sinus 87 (46) Cancer 10 (5)
  Left lateral sinus 81 (43) Malignant hemopathies 19 (10)
  
Straight sinus 28 (15) Thrombophilic abnormalities 37 (20)
  
Cortical veins 16 (9) Recent/ongoing chemotherapy 8 (4)
  Vein of Galen 13 (7) OC* 72 (57)
  Internal cerebral veins 10 (5) HRT* 7 (6)
  
Cavernous sinus 3 (2) Pregnancy* 3 (2)
  
Torcular Herophili 28 (15) Postpartum* 1 (1)
  Left jugular vein 26 (14) Data are expressed as n (%). Forty-seven (25%) patients had >1 known risk
factor for cerebral venous thrombosis. CNS indicates central nervous system;
  Right jugular vein 27 (14) HRT, hormone replacement therapy; and OC, oral contraceptives.
(Continued ) *Percentage calculated in the female subgroup.
 324  Stroke  February 2017

Table 3.  Association of Baseline Characteristics and

Potential Risk Factor for Recurrent VTE at Univariate and
Multivariate Analyses
Variables HR 95% CI P Value
Univariate analysis
 Age, 1-y increment 1.03 (1.00–1.05) 0.026
 Sex, female vs male 1.31 (0.53–2.96) 0.535
 Previous VTE 3.50 (1.44–8.14) 0.0036
 Thrombophilia 0.86 (0.31–2.04) 0.75
 Infection 1.04 (0.30–2.73) 0.95
 Cancer+hemopathies 2.30 (0.76–5.72) 0.099
 Pregnancy+postpartum (n=126) 4.40 (0.69–16.0) 0.052
 OC+HRT (n=126) 0.25 (0.09–0.67) 0.0070
 Unknown cause 2.37 (1.05–5.22) 0.032
Multivariate analysis
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Figure. Kaplan–Meier curve of venous thrombosis ­recurrence  Previous VTE 2.82 (1.14–6.46) 0.018
rate.  Cancer+hemopathies 3.24 (0.98–9.57) 0.039
 Unknown cause 2.81 (1.15–7.04) 0.024
Discussion CI indicates confidence interval; HR, hazard ratio; HRT, hormone replacement
Our study showed that cumulative risk of recurrent VT contin- therapy; OC, oral contraceptive; and VTE, venous thrombotic events.
ues to increase over time. We also detected factors associated
with VT recurrence in subjects who were diagnostically evalu-
ated and treated for the initial CVT. during a median follow-up period of 16 months (mean=18.6,
Early recurrence rates in our study are comparable with the SD=11.1).3 Ruling out subjects lost to follow-up immediately
results of other studies.3–5,7,9–11 Details on the studies that eval- after discharge (n=80), cerebral and extracerebral venous
uated venous thrombotic events recurrence in CVT patients thrombotic recurrence rates were 2.6% and 3.4%, respectively.
are displayed in Table 4.
Similarly, Gosk-Bierska et al4 found a 2.2% annual sinus
In the ISCVT study (International Study on Cerebral Vein
and Dural Sinus Thrombosis), a large prospective multi- thrombosis recurrence rate and a 2.8% annual extracerebral
national observational study conducted on 624 adult cases thrombosis (ie, DVT or PE) recurrence rate during a mean
of CVT, a 2.2% overall CVT recurrence rate and 3% extra- follow-up period of 36±47 months (range 0–262 months) after
cranial venous thrombotic recurrence rate were observed a CVT, with a median time to recurrence of 10 months.

Table 4.  Summary of Studies That Evaluated VTE Recurrence in CVT Patients
Year of Median/
Author Publication Country Study Design Setting Subjects, n Mean FU Definition of Recurrence
Preter et al 9
1996 France Retrospective Tertiary center 77 6.5 y Interview or questionnaire
Ferro et al10
Tertiary centers and community
2002 Portugal Mixed 126 1.8 y Clinical visit or interview
hospitals
Gosk-Bierska et al4 2006 United States Retrospective Tertiary center 154 3y Clinical visit
Miranda et al 6
Tertiary centers and community
2010 Multinational Prospective 624 1.2 y Clinical visit
hospitals
Martinelli et al5 2010 Italy Prospective Tertiary center 145 6y Clinical visit or interview
Dentali et al 7
Tertiary centers and community Clinical visit or interview or
2012 Multinational Retrospective 706 3.3 y
hospitals questionnaire and hospital records
Hiltunen et al11
2016 Finland Retrospective Tertiary center 161 3.2 y Questionnaire

Tertiary center and community

Present study 2016 France Prospective 187 6.7 y Clinical visit or interview
hospitals
 Palazzo et al   Venous Thrombotic Recurrence After CVT    325

An annual CVT recurrence rate of 1.8% was observed by
Preter et al9 in 77 patients with CVT during a median follow-
up period of 63 months, mainly (89%) occurred within the
first 12 months, whereas in the VENOPORT study (Cerebral
Venous Thrombosis Portuguese Collaborative Study Group),
a 1.6% overall CVT recurrent thrombosis rate was reported in
126 CVT patients with a mean follow-up length of 1.8 years.10
Similarly, Martinelli et al5 found an event rate of 2.03 per
100 patient-years in a population of 145 patients with a first
episode of CVT followed up for 6 years after discontinuation
of anticoagulant therapy.
In a large, retrospective cohort study, an overall recurrence
incidence of 23.6 events per 1000 patient-years (95% confi-
dence interval [CI], 17.8–28.7) was observed during a median
follow-up period of 40 months (range 6–297 months).7
Recently, in a retrospective single-center study conducted
on 161 CVT patients with a median follow-up period of 39
months (interquartile range 14–95 months), Hiltunen et al11
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95% CI, 1.25–5.83; P<0.011) has previously been observed
by Dentali et al,7 while the association with cancer was found
only in the univariate analysis.
On the contrary, in the ISCVT, male sex (HR, 2.6; 95% CI,
1.4–5.1; P=0.004) and polycythemia/thrombocythemia (HR,
4.4; 95% CI, 1.6–12.7; P=0.005) were the only independent
predictors of venous thromboembolism after CVT.6
Similarly, in the study conducted by Martinelli et al,5 male
CVT patients had a 7- to 8-fold increased risk of recurrence
compared with female patients, while severe thrombophilia
was associated with an increased risk of DVT or PE (HR,
4.71; 95% CI, 1.34–16.5), but not with CVT recurrence.
However, these findings may not be applicable to the general
CVT population because patients with malignancies or in
need of permanent anticoagulation were not included in this
study. Differences in the inclusion criteria might be the reason
of the discrepancy between our results and those of the Italian
group because we did not find any correlation between sex and

observed a 1.1% annual venous thromboembolic recurrence recurrence risk.

rate (5 DVT, 2 PE, and 3 superficial vein thrombosis) with
a 0.1% annual CVT recurrence rate. Authors stated that low
incidence of recurrence could be explained by the frequent
use of antithrombotic agents in this study population because
39% of patients received permanent anticoagulation and 25%
received aspirin.
Similarly to other studies, in our population, new venous
thrombotic events mainly (52%) occurred in the first 24
months.
In our cohort of CVT patients with long-term follow-up,
subjects with a previous venous thrombotic event, presence of
cancer or malignant hemopathies, and unknown CVT causes
were found to be at higher risk of recurrence in the multivari-
ate analysis.
The increased risk of both cerebral and extracerebral
venous thrombotic recurrence in CVT patients with a history
of previous extracerebral venous thrombotic events (HR, 2.70;
In the study by Gosk-Bierska et al,4 no variable was found
to be significantly associated with recurrent VT, whereas
Hiltunen et al11 did not specifically address this issue.
To our knowledge, this is the first time that cryptogenic
CVT was found to be associated with the risk of recurrence.
The prospective design and long-term follow-up of our study
might explain this difference. Our cryptogenic CVT rate
is similar to that reported in other studies; however, a wide
range of idiopathic thrombosis rates, from 9% to 44%, has
been reported.3–5,7,11 In our opinion, unknown causes may limit
secondary prevention measures in this subgroup of patients,
leading to an increase in the risk of recurrence. This finding
underscores the need for further research to better identify
both congenital and acquired VT risk factors to develop more
specific treatment strategies.
Another finding of our study is that women receiving hor-
monal agents such as oral contraceptives or replacement therapy

Cerebral/Extracerebral VTE Thrombophilia

Annual Recurrence Rate Testing Reported New Cerebral/Extracerebral VTE Factors Associated With VTE Recurrence
1.8%/* Not specified 9 CVT* NA

NA Incomplete 2 CVT2 DVT1 PE NA

2.2%/2.8% Complete 23 VTE occurred in 20 subjects: 10 CVT, 8 DVT, and 5 PE No associated factors
1.5%4.1% overall VTE annual 38 VTE occurred in 36 subjects: 14 CVT, 16 DVT, 4 PE, 3 upper Male sex; polycythemia/
Incomplete
recurrence rate limb DVT, and 1 mesenteric venous thrombosis thrombocythemia
0.53%/1.05% Complete 15 VTE occurred in 15 subjects: 5 CVT, 8 DVT, and 2 PE Male sex; severe thrombophilia
2.4% overall VTE annual
Incomplete 77 VTE occurred in 75 subjects: 31 CVT and 46 extracerebral VTE Previous extracerebral VTE; cancer†
recurrence rate
9 VTE occurred in 9 subjects: 1 CVT, 5 DVT, 2 PE, and 3
0.1%/1.1% Not specified NA
Superficial vein thrombosis
Previous VTE; cancer, malignant
30 VTE occurred in 25 subjects: 6 CVT, 16 DVT, 6 PE, and 2 Portal
0.5%/1.7% Incomplete hemopathies, or JAK2 mutation;
vein thrombosis
unknown CVT causes
CVT indicates cerebral venous thrombosis; DVT, deep vein thrombosis; FU, follow-up; PE, pulmonary embolism; NA, not assessed; and VTE, venous thrombotic events.
*Not known the exact number/incidence of new extracerebral VTE (11 arterial or venous extracerebral events).
†Association found only in the univariate analysis.
 326  Stroke  February 2017
at the time of their first CVT event had lower recurrence risk
compared with women who had not taken estrogens. These data
suggest that subjects whose CVT is favored by hormonal agents
are at lower risk of new venous thrombotic events after estro-
gen discontinuation compared with CVT patients with other
risk factors or whose CVT cause was not detected. Similar data
were obtained in a study conducted on patients with a first event
of DVT and PE; a trend toward a lower risk of recurrence after
discontinuation of oral contraceptive was observed compared
with subjects who had not taken estrogens, although this result
was not confirmed for postmenopausal hormones.12
One limitation of our study is that we included patients
with incomplete thrombophilia evaluation. In fact, because of
a relatively high percentage of subjects whose thrombophilic
screening was not repeated after anticoagulation interruption,
a decision was made to only consider clear prothrombotic
abnormalities. As a consequence, idiopathic CVT percent-
age may have been slightly overestimated. However, because
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of the rigorous selection process and considering the robust
statistical results, we think that our findings were not sig-
nificantly affected. Another limitation is that, because of the
low number of female subjects under replacement therapy
before CVT, we cannot exclude the possibility that the sig-
nificant association between hormonal agents and recurrence
risk was mainly driven by oral contraceptives more than by
postmenopausal hormones. A third limitation is that our study
is a French single-region study, which almost exclusively
included white patients; we cannot rule out the possibility that
our results were influenced by genetic and environmental fac-
tors and, therefore, should be verified in different populations
before being applied to other contexts. However, this design
assures better homogeneity in selection and follow-up proce-
dures. A forth limitation is represented by the higher cancer
and hematology malignancy prevalence compared with previ-
ous follow-up study populations; this probably explains the
relatively high mortality rate during follow-up. However, a
decision was made to include all consecutive subjects with a
first CVT event and at least 1 follow-up evaluation, including
those with malignancies, to better evaluate recurrence rate in
the global CVT population.
Finally, it is worth specifying that all new qualifying events,
including PE, occurred after CVT resolution at follow-up
imaging and should thus be considered as new events and not
as a possible direct consequence of CVT. In fact, PE has been
described in CVT patients even in the absence of DVT, prob-
ably as a consequence of a detached thrombus from the lateral
sinus in subjects with a global prothrombotic state in patients
without thrombosis resolution.13,14
Our study provides data that could contribute to the detec-
tion of subjects at higher risk of venous thrombotic recur-
rence, who may benefit from prolonged anticoagulation.
Acknowledgments
We are grateful to Pr Andrei V. Alexandrov for his precious comments
and suggestions.
Disclosures
None.
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 Venous Thrombotic Recurrence After Cerebral Venous Thrombosis: A Long-Term
Follow-Up Study
Paola Palazzo, Pierre Agius, Pierre Ingrand, Jonathan Ciron, Matthias Lamy, Aline Berthomet,
Paul Cantagrel and Jean-Philippe Neau
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Stroke. 2017;48:321-326; originally published online December 15, 2016;

doi: 10.1161/STROKEAHA.116.015294
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