J Neurooncol (2013) 111:295301
DOI 10.1007/s11060-012-1011-4
CLINICAL STUDY
Clinical manifestation of cancer related stroke: retrospective
casecontrol study
Jeong-Min Kim Keun-Hwa Jung
Kee Hong Park Soon-Tae Lee Kon Chu
Jae-Kyu Roh
Received: 26 April 2012 / Accepted: 20 November 2012 / Published online: 9 January 2013
Springer Science+Business Media New York 2013
Abstract Cancer related stroke may have different pheno-
types from non-cancer stroke, especially in terms of stroke
progression and recurrence. We performed a casecontrol
study to identify their incidences and risk factors in cancer
related stroke. Between January 2001 and December 2009, we
conducted a retrospective review of acute ischemic stroke
patients with cancer who were admitted to Seoul National
University Hospital, Seoul, Korea. The stroke patients without
cancer served as control. We collected demographic variables,
vascular risk factors, stroke phenotype, clinical course, and
cancer information including diagnosis, stage, and treatment
status. Among cancer stroke patients, the potential risk factor of
stroke recurrence was evaluated. The mean age of the 102
cancer patients was 66.4 10.8 years, and 64.7 % were men.
The mean time interval from cancer diagnosis to stroke onset
was 39.7 60.9 months. The principal lesion pattern of can-
cer stroke was multiple dots extending single vascular territory
(39.2 %), and they were associated with low hemoglobin and
high fibrinogen levels. Stroke progression and recurrence were
noted in 9.8 and 27.5 % of cancer stroke patients, and in 9.3 and
12.7 % of control patients, respectively. The stroke subtype
was independently associated with recurrence of cancer stroke
after multiple logistic regression (odds ratio = 3.165, 95 %
confidence interval = 1.0809.277, p = 0.036). Cancer rela-
ted stroke has a distinct phenotype in terms of infarction pattern
and laboratory findings. Stroke recurrence is frequently
observed among cancer stroke patients, and its risk is related
with stroke subtype.
J.-M. Kim
K.-H. Jung
K. H. Park
S.-T. Lee
K. Chu

J.-K. Roh (&)
Stroke & Stem Cell Laboratory, Department of Neurology,
Clinical Research Institute, Seoul National University Hospital,
28, Yongon-dong, Chongro-gu, Seoul 110-744, South Korea
e-mail: rohjk@snu.ac.kr
Keywords Cerebral infarction
Cancer
Recurrence
Introduction
Stroke and cancer are devastating diseases with significant
mortality and morbidity in aged populations. Stroke can
manifest as direct or indirect cancer effects, namely can-
cer related stroke. As cancer treatment improves and
patients survive longer, it is inevitable that cancer patients
suffering from stroke will increase in the future [1, 2].
Cancer related stroke has attracted research interest
because of its distinctive pathomechanism and clinical/
radiologic characteristics [2, 3]. Initial studies focused on
pathologic features of cancer stroke from postmortem
autopsy findings [4], and recent studies described the
relationship between brain magnetic resonance imaging
(MRI) findings and laboratory data [57]. However, few
studies have focused on clinical course of cancer stroke,
probably due to the small number of patients and cross-
sectional study design. Only one group reported that
stroke patients with cancer had higher mortality than
general stroke patients because of poor general health
status by malignancy [6].
Early progression and recurrence of stroke are major
contributing factors affecting functional outcome of stroke
survivors [8, 9]. Cancer related stroke may have different
phenotypes from general stroke in terms of stroke pro-
gression and recurrence, but few studies have focused on
their incidences and risk factors. In this study we con-
ducted a retrospective review of cancer patients diagnosed
with acute ischemic stroke to evaluate clinical and
radiological characteristics, and to find risk factors of
stroke recurrence.
123
296
Methods
Patient inclusion
Between January 2001 and December 2009, patients
aged C 20 years who were diagnosed with acute ischemic
stroke at Seoul National University Hospital, Seoul, Korea,
were eligible for the study, and patients with new or pre-
viously diagnosed cancer were considered as cancer related
stroke patients (CSP). The stroke patients without cancers
were selected consecutively between June and December
2009 as a control group. Stroke was defined using World
Health Organization criteria, and stroke subtypes were
assigned using the Trial of Org 10172 in Acute Stroke
Treatment (TOAST) criteria with slight modification [10,
11]. Stroke patients with large artery disease, cardioem-
bolism, small vessel occlusion, and two or more of them
from TOAST criteria were categorized as conventional
stroke, and the patients who could not fulfill the afore-
mentioned criteria and had other determined etiology or
negative findings from etiology study were assigned as
unconventional. We excluded those patients with hemor-
rhagic stroke, stroke combined with hematologic malig-
nancy, and patients without clinical and radiological data.
When a stroke patient was admitted, we performed brain
MRI and time of flight MR angiography including diffu-
sion weighted image and gradient echo planar image to
confirm stroke location and mechanism, as well as routine
blood tests and coagulation studies. Electrocardiogram and
two-dimensional echocardiography were routinely per-
formed and transesophageal echocardiography or 24-h
electrocardiogram monitoring was performed when nec-
essary. All the patients received standard and best medical
treatment during hospitalization.
Demographic and clinical characteristics
We collected demographic data such as age and gender,
vascular risk factors including hypertension, diabetes,
smoking, and heart disease, stroke location from brain
imaging, and clinical course including symptom severity,
progression, and recurrence. We also reviewed patients
cancer diagnosis, stage, and treatment status. Hyperten-
sion was defined as being present if the patient had
systolic blood pressure [140 mmHg or a diastolic blood
pressure [90 mmHg, or had history of diagnosis of
hypertension or on antihypertensive medication. Diabetes
mellitus was diagnosed as present when a patient had
fasting blood sugar level exceeding 7.0 mmol/L
(126 mg/dL), or had a history of diagnosis of diabetes
mellitus or on oral hypoglycemic agent medication.
Hyperlipidemia was diagnosed when a patient had low
density lipoprotein level exceeding 160 mg/dL or total
123
J Neurooncol (2013) 111:295301
cholesterol level [240 mg/dl, or history of diagnosis of
hyperlipidemia, or was receiving lipid lowering medi-
cation. Heart disease was defined to include coronary
artery disease, atrial fibrillation, valvular heart disease,
and congestive heart failure. Smoking was assigned as
positive when a patient was a current smoker or had quit
smoking within the previous 1 year. Functional outcome
after stroke was measured in terms of National Institutes
of Health Stroke Scale (NIHSS) and modified Rankin
Scale (mRS). Stroke progression was defined as three
points or greater increase on the NIHSS score for the
first 48 h. Stroke recurrence was defined as any new
symptom and associated brain lesion within 1 year after
the index stroke.
Regarding cancer information, its location was deter-
mined from the primary site, and the stage was classified
into four categories: (1) localized; confined within the
primary site, (2) extended; extending from the primary
origin but without systemic metastasis, (3) systemic; evi-
dence of multiple organ involvement, (4) unknown; no
information because cancer staging work up was not per-
formed due to terminal stage. Cancer treatment status
included surgery, chemotherapy, radiotherapy, combined
therapy, and no treatment. We also obtained the total
number of cancer patients concerning each organ who were
maintaining regular follow-up at Seoul National University
Hospital to approximate the cancer stroke prevalence of
each cancer subtype. This study was reviewed and
approved by Institutional Review Board of Seoul National
University Hospital (number: 1004-025-315).
Statistical analysis
Categorical variables are presented as absolute and relative
frequency, and continuous values are shown as
mean standard deviation. We initially tested any dif-
ference between CSP and control stroke patients with v2
test for categorical variables, and by t test for continuous
variables. Stroke subtype was compared as conventional
versus unconventional, and lesion pattern was dichoto-
mized as single lesion versus multiple lesions. Secondly,
we analyzed CSP to find potential risk factors of stroke
recurrence. Fishers exact test and MannWhitney U test
were performed to evaluate risk factors of stroke recur-
rence within CSP. Cancer stage and treatment status were
dichotomized as localized versus non-localized, and as
treatment versus no treatment, respectively. We then per-
formed multiple logistic regression analysis for dichoto-
mized outcome of stroke recurrence. In stroke recurrence,
age, stroke type, extracranial stenosis, and cancer treatment
state were included in the model. Significance was set at
the two tailed p value \ 0.05. All the statistical analyses
were performed using SPSS 18 (SPSS, Chicago, IL).
J Neurooncol (2013) 111:295301 297

Results Table 1 Characteristics of cancer stroke patients and controls

Cancer Control p value
Cancer stroke characteristics stroke stroke

Total of 116 stroke patients was combined with cancer at Patient number 102 171
stroke onset. Among those patients, 11 patients with hemor- Demographic variable
rhagic stroke and 3 patients with hematologic malignancy Age (years) 66.4 10.8 64.4 11.8 0.175
were excluded in our study, and finally 102 patients were Gender (male) 66 (64.7) 107 (62.6) 0.795
reviewed in this study. The mean age of the CSP was Cardiovascular risk factors
66.4 10.8 years and 64.7 % of the patients were male Hypertension 53 (52.0) 110 (64.2) 0.100
(Table 1). Brain MRI of CSP showed distinctive findings Diabetes mellitus 24 (23.5) 56 (32.7) 0.179
(Fig. 1). The most common lesion pattern among CSP was Dyslipidemia 17 (16.7) 37 (21.6) 0.396
multiple dots that were not confined within a single vascular Smoking 40 (39.2) 45 (26.3) 0.061
territory (39.2 %), and the unconventional subtype (25.5 %) Heart disease 23 (22.5) 45 (26.3) 0.482
was more prevalent in CSP than in control group. On the other Stroke type
hand, control stroke patients more frequently had large artery Conventional 76 (75.5) 164 (96.1)
atherosclerosis, and small vascular pathologies including Unconventional 26 (25.5) 7 (3.9) \0.001*
periventricular white matter change and old lacunes than did Stroke lesion pattern
CSP. Hemoglobin level was significantly lower in CSP than No lesion 8 (7.8) 24 (14.0)
in control patients (p = 0.005) and fibrinogen level tended to Anterior territory 29 (28.4) 79 (46.2)
be higher in CSP (p = 0.05). The prevalence of vascular risk Posterior territory 25 (24.5) 54 (31.6)
factors and stroke severity in terms of NIHSS were not dif- Multiple territory 40 (39.2) 14 (8.2) \0.001*
ferent between the two groups. Although stroke progression Functional outcome
was not different between the CSP and control patients (9.8 NIH stroke scale 5.9 5.7 4.8 4.7 0.102
vs. 9.4 %), stroke recurred more commonly in CSP than in Symptom progression 10 (9.8) 16 (9.4) 0.903
control group (27.5 vs. 12.9 %; p = 0.003). Six patients died Stroke recurrence 28 (27.5) 22 (12.9) 0.003*
during hospitalization in each group. More CSP did not Laboratory finding
receive antithrombotic treatment than control stroke patients Hemoglobin (g/dL) 12.2 2.4 13.1 1.8 0.005*
because of terminal cancer state (12.8 vs. 1.2 %; p \ 0.001). C-reactive protein (mg/dl) 0.98 1.49 1.09 1.76 0.646
Fibrinogen (mg/dL) 387 123 359 97 0.050
Combined cancer status Brain imaging finding
Intracranial stenosis 34 (33.3) 90 (52.6) 0.016*
The most common malignancy among CSP was stomach Extracranial stenosis 25 (24.5) 45 (26.3) 0.976
cancer (17.7 %), followed by genitourinary cancer (14.7 %), White matter change 0.6 2.0 7.6 28.7 0.017*
lung cancer (12.7 %), pancreatico-biliary cancer (12.7 %), and volume (mm3)
brain neoplasm (11.8 %) (Table 2). When compared with the Microbleeds on T2* 1.2 3.6 1.8 5.1 0.360
total number of cancer patients, the ratio of cancer stroke was gradient echo
high in patients with brain tumor (0.24 %) and pancretico- Old lacunes 0.1 0.4 0.7 1.1 \0.001*
biliary (0.14 %), and low in breast cancer patients (0.01 %). Stroke treatment
Cancer stage was confined within the primary site in 49 patients Antiplatelet 69 (67.6) 129 (75.4)
(48.0 %), and the other patients had local invasion or systemic Anticoagulant 17 (16.7) 32 (18.7)
metastasis. Three patients had limited staging work-up due to Combination of both 3 (2.9) 8 (4.7)
terminal stage and they were included in systemic group when No treatment 13 (12.8) 2 (1.2) \0.001*
performing statistical analysis. The patients combined with
* Statistically significant difference (p \ 0.05)
extended or systemic cancer had lower hemoglobin level than
the patients with localized malignancy (p = 0.001). Various (39.4 %) experienced stroke within 1 year, and nine out of ten
treatment options including surgery, chemotherapy, radio- patients (90 %) who did not receive any anticancer treatment
therapy or combination of them were performed in CSP, but 10 experienced stroke within 1 year.
patients (9.8 %) did not receive anticancer treatment because
of terminal disease status. The mean time period from cancer Stroke recurrence among CSP
diagnosis to stroke onset was 39.7 60.9 months, and vari-
able according to cancer treatment status (Table 3). Among the Stroke recurrence was reported in 28 patients and was related
38 patients who had received surgical treatment, 15 patients with the number of microbleeds, extracranial stenosis,

123
298 J Neurooncol (2013) 111:295301

Fig. 1 Brain MRI disclosed various lesion patterns of cancer related stroke with unconventional etiology

unconventional stroke etiology, and cancer treatment status Table 2 Cancer characteristics of the 102 cancer stroke patients
(Table 4). After multiple logistic regression, the unconven- Number (%) Total cancer patients
tional etiology (p = 0.036, OR = 3.165, 95 % CI = (CSP %)
1.0809.277) was the only independent variable predicting
Cancer type
recurrence (Table 5), and no treatment of cancer showed a
Stomach 18 (17.7) 27,035 (0.0665 %)
tendency to increase the OR of stroke recurrence (p = 0.086,
Genitourinary 15 (14.7) 29,742 (0.0504 %)
OR = 3.742, 95 % CI = 0.82916.897).
Lung 13 (12.7) 19,542 (0.0665 %)
Pancreatico-biliary 13 (12.7) 9,296 (0.1398 %)
Brain 12 (11.8) 4,955 (0.2422 %)
Discussion
Colon 10 (9.8) 29,358 (0.0341 %)
Head & Neck 9 (8.8) 29,122 (0.0309 %)
This study illustrates the distinct radiological phenotype of
Breast 5 (4.9) 53,006 (0.0094 %)
CSP, which is widespread lesion regardless of single vas-
cular territory. Cancer related stroke was combined with Liver 5 (4.9) 22,984 (0.0218 %)
low hemoglobin and high fibrinogen level; whereas both Musculoskeletal 2 (2.0) 7,534 (0.0265 %)
large artery and small vessel pathologies were less frequent Total 102 (100) 232,574 (0.0439 %)
in CSP than in control patients. Our data also suggest Cancer stage
different stroke prevalence in terms of primary cancer Localized 49 (48.0)
origin. Stroke progression and recurrence among CSP are Extended 23 (22.6)
frequent, and stroke subtype of unconventional etiology is Systemic 27 (26.5)
an independent factor predicting stroke recurrence. Unknown 3 (2.9)
The majority of CSP had widespread multiple lesions Cancer treatment
that were not confined in one vascular territory, and brain Surgery only 38 (37.3)
MRI with diffusion weighted images disclosed that Chemotherapy only 16 (15.7)
infarctions were principally located in multiple end artery Radiotherapy only 3 (2.9)
zones. Intracranial large artery atherosclerosis and small Combination of above 35 (34.3)
vessel disease in terms of old lacune numbers and white No treatment 10 (9.8)
matter hyperintensity volume were less extensive in CSP, CSP cancer stroke patients
implying that conventional vascular pathologies are less
appreciated in cancer associated stroke than distinct cancer
related conditions such as coagulation disorder. The studies [6, 12, 13]. Recently, one group detected multiple
prevalence of vascular risk factors was not different embolic signals from transcranial Doppler and elevated
between the two groups, in agreement with previous serum D-dimer level in CSP, which was attenuated by

123
J Neurooncol (2013) 111:295301 299

Table 3 Time interval between cancer diagnosis and stroke onset

Chemotherapy Surgery Radiotherapy Combination therapy No treatment

Within 1 years 11 15 1 13 9
Within 5 years 4 17 0 12 1
More than 5 years 1 6 2 10 0
Subtotal 16 38 3 35 10
Mean time interval (months) 16.1 22.6 36.1 66.4 115.3 106.1 51.8 63.1 2.8 8.6

Table 4 Factors related to stroke recurrence in patients with cancer- Table 5 Logistic regression analysis of stroke recurrence among
related stroke cancer stroke patients
No recurrence Recurrence p value Odds 95 % Confidence p value
(n = 74) (n = 28) ratio interval

Age (years) 65.3 11.5 69.3 8.2 0.090 Age 1.032 0.9711.098 0.307
Sex (Male) 46 (62.2) 20 (71.4) 0.488 Stroke etiology, 3.165 1.0809.277 0.036
Hypertension 38 (51.4) 15 (53.6) 0.708 unconventional
Diabetes mellitus 17 (23.0) 7 (25.0) 0.794 Extracranial stenosis 2.301 0.7666.910 0.138
Dyslipidemia 12 (16.2) 5 (53.5) 1.000 Cancer treatment, no 3.742 0.82916.897 0.086
therapy
Smoking 28 (37.8) 12 (42.9) 0.656
Heart disease 15 (20.3) 8 (28.5) 0.421
Stroke type 0.181
Conventional 57 (77.0) 16 (57.1) prostate cancer [12]. The difference between studies may
Unconventional 17 (23.0) 12 (42.9) reflect distinct regional cancer prevalence and different
Lesion pattern 0.739 study inclusion criteria. Stomach cancer was the most
Single lesion 47 (63.5) 15 (53.6) common malignancy with stroke in this study, probably
Multiple territory 27 (36.5) 13 (46.4)
because it is the most common cancer in Koreans [15].
NIH stroke scale 5.6 6.6 7.0 6.2 0.285
Brain tumor (0.2422 %) and pancreatico-biliary tumor
Hemoglobin (g/dL) 12.1 2.2 12.3 2.8 0.826
(0.1398 %) patients had relatively higher CSP proportion
than breast cancer patients (0.0094 %), suggesting the
Fibrinogen (mg/dL) 352 100 401 129 0.071
different susceptibility of cancer related stroke. The dif-
Intracranial stenosis 25 (33.7) 11 (39.2) 0.704
ference seems to stem from different cancer cell histology,
Extracranial stenosis 14 (18.9) 12 (42.8) 0.012*
local tumor effect, or treatment modality. Primary brain
White matter volume 0.5 1.7 0.8 2.5 0.475
(mm3) tumor has been associated with an increased risk for stroke,
Microbleeds on T2* 0.5 1.7 2.6 5.7 0.011* mainly from treatment complications such as surgery and
gradient echo radiotherapy [16]. However, it is also probable that cancer
Old lacunes 0.1 0.4 0.1 0.3 0.840 categorization results in a selection bias. For example,
Cancer stage 0.534 many breast cancer patients are diagnosed at an early stage
Localized 38 (51.4) 11 (39.3) by routine healthcare check-up when the systemic effect of
Extended or systemic 36 (48.6) 17 (60.7) cancer is minimal, whereas pancreatico-biliary tumors are
Cancer treatment 0.022* relatively hard to diagnose at an early stage. Patient follow-
Treatment 70 (94.6) 22 (78.6) up status such as death at home or referral to other hospital
No treatment 4 (5.4) 6 (21.4) is another important factor that may distort cancer stroke
prevalence. Studies including multiple centers or with
* Statistically significant difference (p \ 0.05)
prospective design may be necessary to confirm stroke
susceptibility of different cancer origin.
anticoagulation [14]. Based on these findings, it is sug- Cancer stroke patients had lower level of hemoglobin
gested that CSP management should focus on the evalua- than control patients, possibly because cancer patients were
tion of embolic source or hypercoagulable condition. anemic as the result of their chronic disease, and many
Stroke susceptibility seems to be different in terms of patients had gastrointestinal malignancies that were com-
primary cancer location based on our data. A previous monly related with blood loss. The relationship between
study reported that lung cancer is the most common neo- anemia and stroke outcome is controversial in the general
plasm combined with stroke, followed by brain and population, and both low and high hemoglobin levels are

123
300
detrimental to stroke outcome [1719]. In some diseases,
such as sickle cell anemia, a low level of hemoglobin is
associated with increased stroke risk, and transfusion can
attenuate stroke incidence by increasing oxygen carrying
capacity [20, 21]. Further studies are required to confirm
the pathological contribution of anemia in CSP and the
effect of its correction to stroke outcome. We also found
that fibrinogen, which is a coagulation cascade protein,
tended to be increased in CSP than in control patients.
Fibrinogen increase has been reported in stroke patients
and one study reported its association with atherosclerotic
progression and stroke recurrence [22, 23]. Underlying
cancer may have contributed elevated fibrinogen level
because fibrinogen is a reactive protein that can be elevated
in any form of inflammation.
Stroke recurrence is related with a patients functional
outcome and mortality, and attempts to prevent its recur-
rence are essential to minimize neurological deficit after
stroke [24, 25]. Major vessel occlusion, diabetes mellitus,
and low blood pressure have been suggested as a risk factor
of early recurrence among general stroke population [25
27]. In terms of stroke subtypes, large artery disease or
cardioembolism confer a higher risk of recurrence than
other factors in general stroke patients [2830]. However,
those parameters were not evident in cancer related stroke.
The stroke recurrence among CSP was associated with
unconventional stroke etiology, no cancer treatment,
extracranial stenosis, and microbleed number from uni-
variate analysis. Unconventional stroke subtype indepen-
dently predicted stroke recurrence among CSP, and the
difference of vascular pathology was not significant after
adjustment. Hidden embolic source or coagulopathy might
exist among CSP with unconventional etiology, which had
not been disclosed during hospitalization. Since stroke
recurred more commonly among CSP than general stroke
patients, and the portion of unconventional etiology were
considerable (25.5 %), more proactive treatment may be
required for secondary prevention.
Several limitations exist in this study. First of all there is
debate on how to define cancer related stroke, because it
should be differentiated from stroke accidentally combined
with cancer. The causal relationship between the two dis-
eases is sometimes evident in such cases of multiple infarc-
tions in cancer patients without any vascular risk factor, but
strokes combined with clear conventional mechanisms by
TOAST criteria may have little pathologic relationship with
cancer itself [13]. Therefore, unconventional subtype may
represent genuine cancer related stroke. Secondly, selec-
tion bias may exist in stroke detection when cancer patients
refuse brain imaging due to terminal disease status. Since this
study was performed retrospectively, several necessary
information including pathologic and laboratory data such as
D-dimer were not obtained, as well as overall quality of life
123
J Neurooncol (2013) 111:295301
and mortality. Different inclusion time between cancer and
control stroke groups is another weak point of our study,
although stroke diagnosis and treatment strategy were similar
in the two time periods. The relationship between cancer
treatment option and stroke risk is an important issue, but this
study was not able to suggest anticancer treatment effect on
stroke risk because of not enough patients to consider
underlying cancer status, patient condition and combined
vascular risk factors at the same time [31]. Future studies with
larger number of patient inclusion or with homogeneous
cancer patient cohort will disclose possible association
between anticancer treatment and stroke risk.
This study describes distinct clinical characteristics of
stroke patients combined with malignancy, and suggests
possible risk factors of stroke recurrence. Stroke subtypes
and malignancy related conditions may deserve more
attention in predicting stroke outcome than conventional
vascular pathology. Further studies are warranted to dis-
close any modifiable risk factor of recurrence and to sug-
gest better secondary preventive strategy in cancer stroke.
Acknowledgments This study was supported by a grant of the
Korean Health Technology R&D Project, Ministry of Health &
Welfare, Republic of Korea (A110045).
References
1. Wen PY, Glantz MJ (2003) Neurologic complications of cancer.
Preface. Neurol Clin 21:xixiii
2. Grisold W, Oberndorfer S, Struhal W (2009) Stroke and cancer: a
review. Acta Neurol Scand 119:116
3. Rogers LR (2004) Cerebrovascular complications in patients with
cancer. Semin Neurol 24:453460
4. Nguyen T, DeAngelis LM (2006) Stroke in cancer patients. Curr
Neurol Neurosci Rep 6:187192
5. Kwon HM, Kang BS, Yoon BW (2007) Stroke as the first man-
ifestation of concealed cancer. J Neurol Sci 258:8083
6. Zhang YY, Cordato D, Shen Q et al (2007) Risk factor, pattern,
etiology and outcome in ischemic stroke patients with cancer: a
nested case-control study. Cerebrovasc Dis 23:181187
7. Taccone FS, Jeangette SM, Blecic SA (2008) First-ever stroke as
initial presentation of systemic cancer. J Stroke Cerebrovasc Dis
17:169174
8. Petty GW, Brown RD Jr, Whisnant JP et al (2000) Ischemic
stroke subtypes: a population-based study of functional outcome,
survival, and recurrence. Stroke 31:10621068
9. Sumer M, Ozdemir I, Erturk O (2003) Progression in acute
ischemic stroke: frequency, risk factors and prognosis. J Clin
Neurosci 10:177180
10. Aho K, Harmsen P, Hatano S et al (1980) Cerebrovascular dis-
ease in the community: results of a WHO collaborative study.
Bull World Health Organ 58:113130
11. Adams HP Jr, Bendixen BH, Kappelle LJ et al (1993) Classifi-
cation of subtype of acute ischemic stroke: definitions for use in a
multicenter clinical trial TOAST Trial of Org 10172 in Acute
Stroke Treatment. Stroke 24:3541
12. Cestari DM, Weine DM, Panageas KS et al (2004) Stroke in
patients with cancer: incidence and etiology. Neurology 62:
20252030
J Neurooncol (2013) 111:295301
13. Kim SG, Hong JM, Kim HY et al (2010) Ischemic stroke in
cancer patients with and without conventional mechanisms: a
multicenter study in Korea. Stroke 41:798801
14. Seok JM, Kim SG, Kim JW et al (2010) Coagulopathy and
embolic signal in cancer patients with ischemic stroke. Ann
Neurol 68:213219
15. Jung KW, Park S, Kong HJ et al (2011) Cancer statistics in
Korea: incidence, mortality, survival, and prevalence in 2008.
Cancer Res Treat 43:111
16. Kreisl TN, Toothaker T, Karimi S et al (2008) Ischemic stroke in
patients with primary brain tumors. Neurology 70:23142320
17. Huang WY, Chen IC, Meng L et al (2009) The influence of
anemia on clinical presentation and outcome of patients with
first-ever atherosclerosis-related ischemic stroke. J Clin Neurosci
16:645649
18. Tanne D, Molshatzki N, Merzeliak O et al (2010) Anemia status,
hemoglobin concentration and outcome after acute stroke: a
cohort study. BMC Neurol 10:22
19. Irace C, Ciamei M, Crivaro A et al (2003) Hematocrit is asso-
ciated with carotid atherosclerosis in men but not in women.
Coron Artery Dis 14:279284
20. Adams RJ, McKie VC, Hsu L et al (1998) Prevention of a first
stroke by transfusions in children with sickle cell anemia and
abnormal results of transcranial Doppler ultrasonography. N Engl
J Med 339:511
21. Lee MT, Piomelli S, Granger S, STOP Study Investigators et al
(2006) Stroke Prevention Trial in Sickle Cell Anemia (STOP):
extended follow-up and final results. Blood 108:847852
22. Tsuda Y, Satoh K, Kitadai M et al (1997) Hemorheologic profiles
of plasma fibrinogen and blood viscosity from silent to acute and
chronic cerebral infarctions. J Neurol Sci 147:4954
301
23. Audebert HJ, Pellkofer TS, Wimmer ML et al (2004) Progression
in lacunar stroke is related to elevated acute phase parameters.
Eur Neurol 51:125131
24. Thanvi B, Treadwell S, Robinson T (2008) Early neurological
deterioration in acute ischaemic stroke: predictors, mechanisms
and management. Postgrad Med J 84:412417
25. Hillen T, Coshall C, Tilling K et al (2003) Cause of stroke
recurrence is multifactorial: patterns, risk factors, and outcomes
of stroke recurrence in the South London stroke register. Stroke
34:14571463
26. Davalos A, Toni D, Lweins F et al (1999) Neurological deteri-
oration in acute ischemic stroke: potential predictors and asso-
ciated factors in the European cooperative acute stroke study
(ECASS) I. Stroke 30:26312636
27. Ay H, Gungor L, Arsava EM et al (2010) A score to predict early
risk of recurrence after ischemic stroke. Neurology 74:128135
28. Jackson CA, Hutchison A, Dennis MS et al (2009) Differences
between ischemic stroke subtypes in vascular outcomes support a
distinct lacunar ischemic stroke arteriopathy: a prospective,
hospital-based study. Stroke 40:36793684
29. Soda T, Nakayasu H, Maeda M et al (2004) Stroke recurrence
within the first year following cerebral infarctionTottori Uni-
versity Lacunar Infarction Prognosis Study (TULIPS). Acta
Neurol Scand 110:343349
30. Lovett JK, Coull AJ, Rothwell PM (2004) Early risk of recur-
rence by subtype of ischemic stroke in population-based inci-
dence studies. Neurology 62:569573
31. Falanga A, Marchetti M (2012) Anticancer treatment and
thrombosis. Thromb Res 129:353359
123
Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.