Clinical Neurology: Research Article

Eur Neurol Received: April 17, 2020

Accepted: July 27, 2020
DOI: 10.1159/000510627 Published online: October 30, 2020

Assessment of Patients with Intracerebral

Hemorrhage or Hemorrhagic Transformation in the
VENOST Study
Taşkın Duman a Vildan Yayla b Derya Uludüz c Eylem Özaydın Göksu d Vedat Ali Yürekli e
         

Hamit Genç f Uygar Utku g Nilgün Çınar h Hakan Tekeli i Mehmet Ali Sungur j

         

Firdevs Ezgi Tokuç d Nevzat Uzuner k Mehmet Güney Şenol i Arda Yılmaz f Mustafa Gökçe g

         

Seden Demirci e Özge Yılmaz Küsbeci l Gülnur Tekgöl Uzuner k Şevki Şahin m

       

Hale Zeynep Batur Çağlayan n Mustafa Açıkgöz o Fatih Özdağ i Sevim Baybaş p Hakan Ekmekçi q

         

Murat Çabalar b Mehmet Yaman r Hesna Bektaş s Yüksel Kaplan t Başak Karakurum Göksel u

         

Aysel Milanlıoğlu v Dilek Necioğlu Örken w Mehmet Ufuk Aluçlu x Sena Çolakoğlu a

       

Ahmet Tüfekçi y Mustafa Bakar z Bijrn Nazlıel n Nida Taşçılar m Baki Göksan c

         

Hasan Hüseyin Kozak A Handan Mısırlı B Hayriye Küçükoğlu p İpek Midi C Necdet Mengüllüoğlu D

         

Emrah Aytaç E Nilüfer Yeşilot F Birsen İnce c Osman Özgür Yalın G Taşkın Güneş H Serdar Oruç r

           

Füsun Mayda Domaç I Şerefnur Öztürk q Ali Karahan J Hacı Ali Erdoğan b Nazire Afşar K

         

aDepartment
of Neurology, Mustafa Kemal University, Antakya, Turkey; b Clinics of Neurology, University of Health
Sciences Bakirkoy Dr. Sadi Konuk Research and Training Hospital, Istanbul, Turkey; cDepartment of Neurology,
Istanbul Cerrahpasa University, Istanbul, Turkey; dClinic of Neurology, Antalya Research and Training Hospital, Antalya,
Turkey; eDepartment of Neurology, Suleyman Demirel University, Isparta, Turkey; fDepartment of Neurology, Mersin
University, Mersin, Turkey; gDepartment of Neurology, Kahramanmaras Sutcu Imam University, Kahramanmaras,
Turkey; hDepartment of Neurology, Maltepe University, Istanbul, Turkey; iClinic of Neurology, Sultan Abdulhamid
Han Research and Training Hospital, Istanbul, Turkey; jDepartment of Biostatistics, Duzce University, Duzce, Turkey;
kDepartment of Neurology, Osmangazi University, Eskisehir, Turkey; lClinic of Neurology, Bozyaka Education, Research

and Training Hospital, Izmir, Turkey; mDepartment of Neurology, Maltepe University, Istanbul, Turkey; nDepartment of
Neurology, Gazi University, Ankara, Turkey; oDepartment of Neurology, Bulent Ecevit University, Zonguldak, Turkey;
pClinic of Neurology, Bakirkoy Research and Training Hospital for Neurologic and Psychiatric Diseases, Istanbul, Turkey;
qDepartment of Neurology, Selcuk University, Konya, Turkey; rDepartment of Neurology, Kocatepe University, Afyon,

Turkey; sClinic of Neurology, Ataturk Research and Training Hospital, Ankara, Turkey; tDepartment of Neurology, Inonu
University, Malatya, Turkey; uDepartment of Neurology, Baskent University, Adana, Turkey; vDepartment of Neurology,
Yuzuncu Yıl University, Van, Turkey; wDepartment of Neurology, Istanbul Bilim University, Istanbul, Turkey; xDepartment
of Neurology, Dicle University, Diyarbakir, Turkey, Turkey; yDepartment of Neurology, Recep Tayyip Erdogan University,
Rize, Turkey; zDepartment of Neurology, Uludag˘ University, Bursa, Turkey; ADepartment of Neurology, Necmettin
Erbakan University, Konya, Turkey; BClinic of Neurology, Haydarpasa Training and Research Hospital, Health Sciences
University, Istanbul, Turkey; CDepartment of Neurology, Marmara University, Istanbul, Turkey; DClinic of Neurology,
Eskisehir Government Hospital, Eskisehir, Turkey; EClinic of Neurology, Ankara Research and Training Hospital, Ankara,
Turkey; FDepartment of Neurology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey; GClinic of
Neurology, Istanbul Training and Research Hospital, Health Sciences University, Istanbul, Turkey; HClinic of Neurology,
Maltepe Government Hospital, Istanbul, Turkey; IErenkoy Research and Training Hospital for Neurologic and Psychiatric
Diseases, Istanbul, Turkey; JDepartment of Physical Medicine and Rehabilitation, Usak University, Usak, Turkey;
KDepartment of Neurology, Acibadem University, Istanbul, Istanbul, Turkey
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karger@karger.com © 2020 S. Karger AG, Basel Vildan Yayla

www.karger.com/ene Clinics of Neurology, University of Health Sciences
Bakirkoy Dr. Sadi Konuk Research and Training Hospital
Zuhuratbaba mh Tevfik Sağlam cd No:11, Bakırköy, Istanbul 34158 (Turkey)
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Keywords
Cerebral venous thrombosis · VENOST · Cerebral
hemorrhage
Abstract
Introduction: Cerebral venous and sinus thrombosis (CVST)
may lead to cerebral edema and increased intracranial pres-
sure; besides, ischemic or hemorrhagic lesions may devel-
op. Intracerebral hemorrhages occur in approximately one-
third of CVST patients. We assessed and compared the find-
ings of the cerebral hemorrhage (CH) group and the CVST
group. Materials and Methods: In the VENOST study, med-
ical records of 1,193 patients with CVST, aged over 18 years,
were obtained from 35 national stroke centers. Demograph-
ic characteristics, clinical symptoms, signs at the admission,
radiological findings, etiologic factors, acute and mainte-
nance treatment, and outcome results were reported. The
number of involved sinuses or veins, localizations of throm-
bus, and lesions on CT and MRI scans were recorded. Re-
sults: CH was detected in the brain imaging of 241 (21.1%)
patients, as hemorrhagic infarction in 198 patients and in-
tracerebral hemorrhage in 43 patients. Gynecologic causes
comprised the largest percentage (41.7%) of etiology and
risk factors in the CVST group. In the CH group, headache
associated with other neurological symptoms was more fre-
quent. These neurological symptoms were epileptic sei-
zures (46.9%), nausea and/or vomiting (36.5%), altered con-
sciousness (36.5%), and focal neurological deficits (33.6%).
mRS was ≥3 in 23.1% of the patients in the CH group. Dis-
cussion and Conclusion: CVST, an important cause of stroke
in the young, should be monitored closely if the patients
have additional symptoms of headache, multiple sinus in-
volvement, and CH. Older age and parenchymal lesion, ei-
ther hemorrhagic infarction or intracerebral hemorrhage,
imply poor outcome. © 2020 S. Karger AG, Basel
Introduction
Cerebral venous and sinus thrombosis (CVST) is a
rare but important cause of stroke in the young. The
incidence of adult CVST is approximately 1.3 per
100,000 person-years [1–3]. In CVST, ischemic or hem-
orrhagic parenchymal lesions may develop. Intracere-
bral hemorrhages (ICHs) occur in approximately one-
third of CVST patients, with a severe clinical presenta-
tion and worse outcome [4–7]. In this study, we aimed
to present the characteristics of the clinical presenta-
2 Eur Neurol
DOI: 10.1159/000510627
tions, risk factors, neuroimaging features, and clinical
outcomes in patients with cerebral hemorrhage (CH) or
hemorrhagic transformation, who were included in the
VENOST study.
Materials and Methods
The design of VENOST, the list of participating centers and
investigators, and the main results have already been reported
[2]. VENOST is a prospective, multicenter, hospital-based ob-
servational study. In this study, medical records of 1,193 patients
with CVST aged over 18 years were obtained from 35 national
stroke centers. CVST patients were identified by neurologists.
The study was approved by the ethics committee of the coordi-
nating center (No. 83045809/604/02-12333). The diagnosis of
CVST was based on the clinical presentation of patients and
neuroimaging.
Demographic characteristics, clinical symptoms and signs at
the admission, radiological findings, etiologic factors, acute and
maintenance treatment, and follow-up results were reported. As-
sociated illnesses or conditions were also recorded.
Clinical presentations were recorded as headache, nausea
and/or vomiting, seizures, altered consciousness, visual field
disturbances, focal neurological deficit, and cranial nerve in-
volvement. The number of involved sinuses or veins, localiza-
tions of thrombus, and lesions on CT and MRI scans (presence
of parenchymal involvement, ischemic infarction, hemorrhagic
infarction, and ICH) were recorded. Information on acquired or
congenital thrombophilic abnormalities, including antithrom-
bin III, protein C/S deficiency, homocysteine, anti-cardiolipin
and anti-phospholipid antibodies, mutations in the methylene-
tetrahydrofolate reductase (MTHFR) gene, prothrombin gene,
factor V Leiden, or plasminogen activator inhibitor (PAI) gene,
and anti-nuclear antibodies, was collected, if available. All treat-
ment modalities based on physician preference were recorded
[2].
Outcome in the follow-up was categorized by the modified
Rankin scale (mRS). Patients with mRS scores 0–1 were classified
as independent (favorable outcome), mRS score 2 as minimal dis-
ability, and mRS scores 3–6 as dependent or dead (poor outcome).
Follow-up visits were recorded after 1, 3, 6, and 12 months of the
initial diagnosis of CVST, if available, for patients who were fol-
lowed up directly through interviews and observations by the in-
vestigators to determine the periodic results of patients’ function-
al outcome [2].
Statistical Methods
Continuous data were summarized as mean ± standard devia-
tion, and categorical data were presented as frequency and per-
centage. The independent sample t test was used to compare
groups for continuous variables. Categorical data were analyzed by
using Pearson χ2 or likelihood ratio test statistics. Odds ratios (OR)
were calculated for the possible prognostic factors using the mul-
tivariate logistic regression analysis. Statistical analyses were con-
ducted with SPSS v.22 statistical package [2].
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Duman et al.
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 Table 1. The distribution of neurological symptoms

CVST NCH CH p value

(n = 1,144) (n = 903) (n = 241)

Isolated headache, n (%) 287 (25.1) 262 (29.0) 25 (10.4) <0.001

Headache, n (%) 997 (87.2) 794 (87.9) 203 (84.2) 0.128
Nausea and/or vomitting, n (%) 317 (27.7) 229 (25.4) 88 (36.5) 0.001
Epileptic seizure, n (%) 271 (23.7) 158 (17.5) 113 (46.9) <0.001
Visual field defect, n (%) 303 (26.5) 263 (29.1) 40 (16.6) <0.001
Focal neurological deficit, n (%) 208 (18.2) 127 (14.1) 81 (33.6) <0.001
Consciousness disturbances, n (%) 204 (17.8) 116 (12.8) 88 (36.5) <0.001
Cranial nerve palsies, n (%) 128 (11.2) 105 (11.6) 23 (9.5) 0.362

CVST, cerebral venous and sinus thrombosis; NCH, none cerebral hemorrhage; CH, cerebral hemorrhage.

Results Table 2. The distribution of involved sinuses

None Hemorrhagic p value

Among the identified 1,193 CVST patients, a total of (n = 903) (n = 241)
1,144 patients with confirmed CVST diagnosis were re-
cruited. CH was detected in the brain imaging of 241 Isolated transverse sinuses, n (%) 259 (28.7) 33 (13.7) <0.001
(21.1%) patients; 198 patients had hemorrhagic infarc- Isolated sagittal sinuses, n (%) 126 (14.0) 42 (17.4) 0.176
tion, 43 patients had ICH and the rest of the patients (n = Isolated sigmoid sinuses, n (%) 31 (3.4) 6 (2.5) 0.462
Isolated cortical veins, n (%) 14 (1.6) 10 (4.1) 0.012
903, 78.9%) were grouped as the none cerebral hemor- Isolated jugular sinuses, n (%) 16 (1.8) 0 (0.0) 0.031
rhage (NCH) group. Isolated cavernous sinuses, n (%) 8 (0.9) 1 (0.4) 0.694
The rate of female patients was 67.9% in CVST; it was Transverse sinuses, n (%) 666 (73.8) 174 (72.2) 0.627
66.1% in the NCH group and 74.7% in the CH group Sigmoid sinuses, n (%) 351 (38.9) 104 (43.2) 0.227
Sagittal sinuses, n (%) 323 (35.8) 122 (50.6) <0.001
(p = 0.001). The mean age of each group did not show any
Internal jugular vein, n (%) 141 (15.6) 37 (15.4) 0.921
significant difference between the NCH (39.90 ± 13.72 Cortical veins, n (%) 25 (2.8) 17 (7.1) 0.002
years) and CH (40.69 ± 13.64 years) groups (p = 0.426). Cavernous sinuses, n (%) 16 (1.8) 3 (1.2) 0.779
The onset mode was recorded in 1,126 CVST patients:
887 patients in NCH and 239 patients in CH groups.
Acute mode of onset was prominent (69.5%) in the CH
group, but chronic mode of onset was less frequent (6.3%);
in the NCH group, they were 41.0 and 22.3%, respective- ed of CVST. In all of the CVST group, radiological imag-
ly (p < 0.001). ing revealed parenchymal lesions in 459 patients (40.1%),
In our whole CVST (87.2%), NCH (87.9%), and CH and 416 patients (36.4%) had infarction at diagnosis, of
(84.2%) groups, the most common symptom was head- whom 198 were with hemorrhagic transformation (17.3%)
ache (p = 0.128). Isolated headache was detected in 25.1% while 43 patients had hemorrhagic stroke (3.8%).
of the CVST patients and 29% in the NCH group but In the CVST group, venous involvement was found in
10.4% in the CH group (p < 0.001). In the CH group, 1 sinus in 551 patients (48.2%). In the CH group, multiple
headache associated with other neurological symptoms sinuses involvement was more frequent with the 61%
was more frequent than the NCH group. In the CH group, rate, but in the NCH group, 1 sinus involvement was de-
the neurological symptoms were epileptic seizures tected in 49.4% of the patients (p = 0.001). In the CH
(46.9%), nausea and/or vomiting (36.5%), altered con- group, the hemorrhagic infarction group and the hemor-
sciousness (36.5%), and focal neurological deficits (33.6%) rhagic group did not show any significant difference in
(p ≤ 0.001) (Table 1). the number of involved sinuses (p = 0.339) (Table 2).
CVST was diagnosed by cranial MRI and MR venogra- In the CVST group, either by isolated or multiple in-
phy and CT and/or CT venography. The diagnosis of volvement, the transverse sinus was the most common
CVST was established in DSA in 23 patients (2%) suspect- site of thrombosis (73.4%, n = 840). Isolated transverse
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Intracerebral Hemorrhage in the Eur Neurol 3

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 Table 3. The distribution of the laboratory findings

Hem. Inf. Hemorrhage p value

(n = 198) (n = 43)

MTHFR (n = 159)
Heterozygote 5 (3.8%) 0 (0.0%) 0.477
Homozygote 9 (6.9%) 3 (10.7%)
Phrothrombin mutation (n = 159) 6 (4.6%) 3 (10.7%) 0.196
PAI mutation (n = 159) – – –
Factor V Leiden mutation (n = 159) 13 (9.9%) 0 (0.0%) 0.127
Anti-phospholipid Ab (n = 206) 2 (1.2%) 0 (0.0%) 0.696
Hyperhomocysteinemia (n = 206) 12 (7.0%) 2 (5.9%) 0.817
Hyperfibrinogenemia (n = 206) – – –
Protein C/S deficiency (n = 206) 19 (11.0%) 1 (2.9%) 0.209
Activated protein C resistancy (n = 206) 2 (1.2%) 2 (5.9%) 0.128
Antithrombin III deficiency (n = 206) 1 (0.6%) 0 (0.0%) 0.835
ANA (n = 206) 5 (2.9%) 0 (0.0%) 0.593
Thrombocytosis (n = 206) 2 (1.2%) 0 (0.0%) 0.696
Anti-cardiolipin Ab (n = 206) 1 (0.6%) 1 (2.9%) 0.304
Polycythemia vera (n = 206) 2 (1.2%) 0 (0.0%) 0.696

MTHFR, methylenetetrahydrofolate reductase; PAI, plasminogen activator inhibitor.

Table 4. The distribution of treatment Etiology and Risk Factors

In the CVST group, gynecologic causes comprised the
CSVT NCH CH largest group (41.7%). In the CH group, the rate of puer-
(n = 1,144) (n = 903) (n = 241)
perium (23.3%) and oral contraceptives (21.1%) was sig-
No medication nificantly higher than the NCH group (16.8 and 11.7%),
N 507 414 93 respectively (p = 0.001 and p = 0.045). Additionally, the
% 44.3 45.8 38.6 puerperium was more frequent in the hemorrhagic in-
Anticoagulation farction group (27%) than the hemorrhagic group (6.3%)
N 480 353 127
% 42.0 39.1 52.7 (p = 0.012).
Others – unknown Hematological parameters were completed in 941
N 157 136 21 (82.3%) patients, and genetic screening for thrombophil-
% 13.7 15.1 8.7 ia was recorded in 729 patients (63.7%). Prothrombin
mutation, factor V Leiden mutation, and protein C/S de-
CVST, cerebral venous and sinus thrombosis; NCH, none
cerebral hemorrhage; CH, cerebral hemorrhage. ficiencies were significantly higher in the CH group (p =
0.011, p = 0.044, and p < 0.001) (Table 3). There were not
any significant differences between the hemorrhagic in-
farction and hemorrhagic groups (Table 3).
In the NCH group, 45.8% of the patients and, in the
sinus involvement was more frequent in the NCH group CH group, 38.6% of the patients did not have any medica-
(28.7%) compared with the CH group (13.7%) (p < 0.001). tion (p = 0.044); in the NCH group, 36.2% had heparin or
In the CH group, sagittal sinus involvement was signifi- SC anticoagulation, and in the CH group, 49.8% had hep-
cantly more frequent (50.6%) than the NCH group arin or SC anticoagulation (p = 0.000); and the rest of the
(35.8%) (p < 0.001) (Table 2). There were not any signifi- groups had other medications such as acetylsalicylic acid
cant differences between the hemorrhagic infarction or or unknown (Table 4).
hemorrhagic stroke groups for the isolated or multiple mRS score in the first-month visit was available for 216
involvement of sinuses. (87.8%) patients in the CH group. At the first-month vis-
it, in the NCH group, mRS was 0–1 in 83.5% of the pa-
tients, and it was ≥3 in 6.3% of the patients, but in the CH
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4 Eur Neurol Duman et al.

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 Table 5. Univariate and multivariate analysis for risk factors according to higher mRS (≥3) (n = 691)
Univariate
OR
51+/≤50 years 4.278
>2 sinuses involvement 0.898
Parenchymal involvement, yes/no 3.397
Malignancy, yes/no 6.579
OR, odds ratio; mRS, modified Rankin scale.
group, mRS was 0–1 in 59.7% of the patients and ≥3 in
23.1% of the patients (p < 0.001). Between the hemor-
rhagic infarction and hemorrhagic groups, there were no
statistical differences.
A multivariate logistic regression analysis was con-
ducted for the risk factors according to higher mRS (≥3);
older age (≥50 years) (OR = 3.347, 95% CI = 1.407–7.961,
p = 0.006), parenchymal involvement (OR = 3.394, 95%
CI = 1.497–7.697, p = 0.003), and malignancy (OR =
3.657, 95% CI = 1.221–10.951, p = 0.020) were signifi-
cantly associated with higher mRS (Table 5).
Discussion
CVST is an uncommon but potentially serious and
life-threatening cause of stroke [8]. The thrombosis of the
cortical veins and cerebral sinuses can cause an increase
in the venous and capillary pressure causing the break-
down of the blood-brain barrier; consequently, localized
brain edema, ischemic neuronal damage or petechial
hemorrhages, venous infarction, or large hematomas
may develop [3, 9]. ICHs occur in approximately 30–40%
of patients with CVST and is usually associated with a
more severe clinical presentation at onset and a worse
outcome [4, 7, 8, 10]. CH was reported in 39% out of 624
patients in the multicentric ISCVT study [4, 5]. Kumral
et al. [7] reported that 33% of 220 patients had CH. Ac-
cordingly, in our CVST group, CH was detected in 27.5%
of the CVST patients.
In many studies, CVST is three times more common
in women than in men in young adults. Female-specific
risk factors such as oral contraceptive use, hormone re-
placement therapy, and pregnancy/puerperium cause
this divergent ratio [2, 3, 11]. In an Indian study, preva-
lence of CSVT was higher in men (53.7%), and the mean
age was 31.3 years [12]. In another study similar to our
Intracerebral Hemorrhage in the
VENOST Study
Multivariate
95% CI p value OR 95% CI p value
1.936–9.453 <0.001 3.343 1.402–7.971 0.006
0.303–2.656 0.845 0.716 0.232–2.204 0.560
1.535–7.514 0.003 3.506 1.534–8.013 0.003
2.456–17.623 <0.001 3.681 1.221–11.093 0.021
CSVT group, the female ratio was 69% and the mean age
was 44 ± 7 years [7]. In our study, the female ratio was
67.9% in CVST and 66.1% in NCH groups but signifi-
cantly higher in the CH group (74.7%) (p = 0.001). There
was not any significant difference between the mean ages
of NCH (39.90 ± 13.72) and CH (40.69 ± 13.64) groups
(p = 0.426).
Although many studies report acute onset to be more
common, in the study by Sidhom et al. and Wang et al.
[13, 14], it is reported less. In the ISCVT trial, it is report-
ed that the mode of onset was acute in 37.2% of patients
[5]. Girot et al. [4] reported acute onset was detected in
47% of patients with early-ICH, but in patients without
early-ICH, it was 31%. In our study, acute mode of onset
was similar to the ISCVT study in the NCH group (41%)
and higher in the CH group (69.5%), suggesting more se-
vere clinical presentation.
Headache is the commonest presentation of CVST pa-
tients (70–90%) [4, 5, 7, 9, 10, 13, 14]. Most often it is dif-
fuse and severe and has gradual onset, but a subgroup of
patients presents with thunderclap headache, mimicking
subarachnoid hemorrhage [3, 15]. Headache can be iso-
lated or associated with other neurological deficits in
CVST patients. The venous infarcts are often hemorrhag-
ic and cause focal neurological deficits and irritative phe-
nomenon, and thus partial or generalized epileptic sei-
zures can be more frequent [3, 7, 9]. In the ISCVT trial,
approximately 40% of the patients had any type of sei-
zures, 40% had motor deficits, and 14% were stupor or
comatose [5]. In the study by Kumral et al. [7], headache,
sensorial deficits, seizures, dysarthria and aphasia, and
behavioral deficits (anxiety and depression) reported sig-
nificantly higher in patients with hemorrhagic lesion.
Similarly, the most common symptom was headache in
our CVST (87.2%), NCH (87.9%), and CH (84.2%) groups
(p = 0.128). In the CH group, headache was associated
with other neurological symptoms more frequently.
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Again, epileptic seizures (46.9%), nausea and/or vomiting
(36.5%), consciousness disturbances (36.5%), and focal
neurological deficits (33.6%) were significantly higher in
the CH group (p ≤ 0.001).
In the ISCVT study, the most frequently occluded
sinuses were the superior sagittal sinus (62%) and the
lateral sinuses (each around 40%) that were consistent
with other studies [5, 7, 12, 13]. In the VENOST study
and other studies, the most frequently occluded sinuses
were the transverse and sigmoid sinuses, followed by
the superior sagittal sinus [2, 14]. Multiple sinus in-
volvement was reported between 50 and 78% in differ-
ent studies, and a strong correlation was reported be-
tween the multiple sinus involvement and hemorrhagic
lesions [2, 7, 14]. In our study, compatible with other
studies, transverse sinus involvement was common in
both groups; in the CH group, sagittal sinus involve-
ment (50.6%) was significantly more frequent than the
NCH group (35.8%) (p < 0.001). Multiple sinus involve-
ment was more frequent (61.0% rate) in the CH group
(p = 0.001).
The most common risk factors were reported as use
of oral contraceptive (54.3%) and thrombophilia
(34.1%) [5]. The higher incidence of CVST in women
was explained by the female-specific risk factors such as
oral contraceptive use, hormone replacement therapy,
and pregnancy/puerperium [3, 5, 7, 11]. Many other
different genetic or acquired risk factors are associated
with CVST [3, 5, 16]. One risk factor can be identified
in 85% of the patients and >1 factors in 44% [17]. In the
VENOST study, at least one sex-related risk factor was
detected in 41.7% of the patients, the risk was the high-
est in the post-partum period, and prothrombotic fac-
tors were present in 26.4% of the patients [2]. Compat-
ible with previous studies, female-specific risk factors
such as oral contraceptive use, puerperium, and pro-
thrombotic factors were significantly higher in the CH
group. Moreover, puerperium was significantly higher
in the hemorrhagic infarction group than the hemor-
rhagic group (p = 0.012).
The prognosis of CVT is generally good, 80% of the
patients recover [3, 5, 18]. In the Dutch-European Cere-
bral Sinus Thrombosis Trial, coma and CH were the in-
dependent predictors of a bad outcome [19]. In VENO-
PORT, ISCVT, and some other studies, the rate of depen-
dency or death was reported as 4–21% [4–6]. But, in
recent studies, the mortality rate was 1% at discharge and
3% at follow-up [1, 7]. This decline in mortality rate was
attributed to an increased awareness of CSVT, a better
therapy, and a better diagnosis with more developed neu-
6 Eur Neurol
DOI: 10.1159/000510627
roimaging techniques which led to the identification of
less severe cases [1, 3, 5]. A recent study showed that pa-
tients with hemorrhagic lesion had a worse prognosis in
the acute phase and at the end of follow-up [20]. In Kum-
ral et al. [7]’s series, the patients with hemorrhagic infarc-
tion and ICH had more severe disability (42%) or death
rate (35%) (mRS 3–6). They concluded that hemorrhage
itself is an independent predictor for a poor clinical out-
come [7]. In our study, in the CH group, mRS ≥3 was
found in 23.1% of the patients, but in 6.3% of the NCH
group (p < 0.001), which imply worse prognosis in the CH
group.
Current AHA/ASA guidelines recommend anticoagu-
lation for patients with CVT and ICH, and once CVT di-
agnosis has been confirmed, treatment with anticoagula-
tion should be initiated regardless of the presence of pre-
treatment ICH. The data do not support any differences
in outcome with the use of unfractionated or low molec-
ular weight heparin in CVT patients [8]. In the ISCVT
study, >80% of the patients had anticoagulation therapy.
In Kumral et al. [7]’s study, 79% of all the CVT patients
and 81% of the hemorrhagic patients had anticoagulation
therapy, but they reported that anticoagulation or conser-
vative treatment did not make statistically significant dif-
ference on the death rate of CVT patients. But, they stat-
ed that the death rate in patients with hemorrhagic lesion
was more frequent but statistically insignificant [7]. In
our study, anticoagulation therapy was significantly high-
er in the CH group. Multivariate logistic regression anal-
ysis showed older age (≥50 years), parenchymal involve-
ment, and malignancy were significantly associated with
higher mRS.
Conclusion
CVST, an important cause of stroke in the young,
should be monitored closely if the patients have addition-
al symptoms of headache, multiple sinus involvement,
and CH. Older age and parenchymal lesion, either hem-
orrhagic infarction or ICH, imply poor outcome.
Statement of Ethics
The study was approved by the ethics committee of the coordi-
nating center (No. 83045809/604/02-12333). This study complies
with the guidelines for human studies and animal welfare regula-
tions.
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Duman et al.
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 Conflict of Interest Statement
There are no conflicts of interest. The authors certify that they
have no affiliations with or involvement in any organization or
entity with any financial interest (such as honoraria; educational
grants; participation in speakers’ bureaus; membership, employ-
ment, consultancies, stock ownership, or other equity interests;
and expert testimony or patent-licensing arrangements).
Author Contributions
Conception: Prof. Taşkın Duman, MD; Prof. Derya Uludüz,
MD; Prof. Nevzat Uzuner, MD; Prof. Vildan Yayla, MD; Prof. Baki
Göksan, MD; Prof. Birsen İnce, MD; and Prof. Şerefnur Öztürk,
MD. Design: Eylem Özaydın Göksu, PhD; Prof. Vildan Yayla, MD;
Assoc. Prof. Murat Çabalar, MD; Prof. Mehmet Yaman, MD; Prof.
Başak Karakurum Göksel, MD; Prof. Bijrn Nazlıel, MD; and
Taşkın Güneş, PhD. Supervision: Prof. Vildan Yayla, MD; Prof.
Fatih Özdağ, MD; Assoc. Prof. Vedat Ali Yürekli, MD; Hamit
GENÇ, PhD; Assoc. Prof. Gülnur Tekgöl Uzuner, MD; and Assoc.
Prof. Hasan Hüseyin Kozak, MD. Materials: Uygar Utku, PhD;
Prof. Şevki Şahin, MD; Asst. Prof. Hakan Ekmekçi, MD; Hesna
Bektaş, PhD; Mehmet Ufuk Aluçlu, MD; Prof. Nida Taşçılar, MD;
Necdet Mengüllüoğlu, PhD; and Emrah Aytaç, PhD. Data collec-
tion and/or processing: Assoc. Prof. Hakan Tekeli, MD; Mehmet
Ali Sungur, PhD; Assoc. Prof. Sevim Baybaş, MD; Hayriye
Küçükoğlu, PhD; Prof. Nilüfer Yeşilot, MD; and Osman Özgür
Yalın, PhD. Analysis and/or interpretation: Firdevs Ezgi Tokuç,
PhD; Prof. Mehmet Güney Şenol, MD; Assoc. Prof. Yüksel Kaplan,
MD; Asst. Prof. Ahmet Tüfekçi, MD; Prof. Mustafa Bakar, MD;
Asst. Prof. Serdar Oruç, MD; and Assoc. Prof. Füsun Mayda
Domaç, MD. Literature review: Prof. Arda Yılmaz, MD; Prof.
Mustafa Gökçe, MD; Prof. Handan Mısırlı, MD; Asst. Prof. Seden
Demirci, MD; Prof. Dilek Necioğlu Örken, MD; and Prof. İpek
Midi, MD. Writing: Assoc. Prof. Özge Yılmaz Küsbeci, MD; Prof.
Vildan Yayla, MD; Prof. Fatih Özdağ, MD; Hacı Ali Erdoğan, MD;
and Prof. Nazire Afşar, MD. Critical review: Assoc. Prof. Nilgün
Çınar, MD; Asst. Prof. Hale Zeynep Batur Çağlayan, MD; Asst.
Prof. Mustafa Açıkgöz, MD; Assoc. Prof. Aysel Milanlıoğlu, MD;
and Assoc. Prof. Ali Karahan, MD.

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Intracerebral Hemorrhage in the Eur Neurol 7

VENOST Study DOI: 10.1159/000510627
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