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Role of Blood Biomarkers in
Differentiating Ischemic Stroke and
Intracerebral Hemorrhage
Rohit Bhatia, Anand R Warrier, Vishnubhatla Sreenivas1, Prerna Bali, Pranjal Sisodia,
Anchal Gupta2, Nishita Singh, M V Padma Srivastava, Kameshwar Prasad

DOI:
10.4103/0028-3886.293467
Abstract:
PMID: Background and Purpose: Although imaging is the mainstay to differentiate ischemic stroke (IS) from
xxxx intracerebral hemorrhage (ICH), these facilities are not available everywhere. The present study observed if any
blood biomarker(s) could potentially help differentiate between ischemic stroke and intracerebral hemorrhage.
Methods: 250 patients with acute stroke within 24 hours of onset (187 IS and 63 patients with ICH) were
recruited in the present study. The blood samples were collected closest to the hospital presentation time,
but within 24 hours of stroke onset. Blood was analyzed for five biomarkers  [S100, glial fibrillary acidic
protein (GFAP), N‑methyl‑D‑aspartate receptor subunit antibody (NR2), interleukin 6 (IL6) and brain natriuretic
peptide (BNP)] to assess discriminatory ability of each biomarker to differentiate ICH and IS.
Results: S100 levels were statistically higher among patients with ICH compared with IS (8 pg/ml versus 4.2
pg/ml respectively, P = 0.003) and IL6 was higher in patients with IS compared with ICH (12.9 pg/ml vs 8.76
pg/ml, P = 0.02). The discriminatory ability to differentiate ICH from IS was better using a combination of the
above two biomarkers. The overall discriminatory ability of all biomarkers were low (Area under curve for
S100 65%; GFAP 56%; NR2 53%; IL6 59% and BNP 49.8%). Although the positive predictive value of each
biomarker was low, the negative predictive value was higher for all biomarkers to diagnose ICH.
Conclusions: S100 and IL6 are potential biomarkers for further study and validation. Newer biomarkers with
higher discriminatory ability are required in the future for diagnostic use.
Key Words:
Biomarkers, BNP, GFAP, ICH, Ischemic stroke, NR2, S100

Key Message:
Differentiating stroke subtype is critical for timely decision of specific management. Blood biomarkers could
have a potential role in differentiating ischemic stroke from intracerebral hemorrhage. S100, IL6, GFAP, NMDA
NR2 subunit, BNP are biomarkers that have been investigated. Overall discriminatory ability of biomarkers
was low but could improve using combination of biomarkers. S100 and IL6 are potential biomarkers that need
further study and vaildation.

S troke accounts for the second leading cause

of death and disability around the world.
Early diagnosis of stroke is imperative to provide
stroke subtypes including thrombolysis, blood
pressure reduction etc.[4] Although imaging is the
mainstay of differentiating ischemic stroke (IS)
timely and appropriate care.[1,2] Although the from intracerebral hemorrhage  (ICH), these
Departments diagnosis of stroke is clinical, recognizing and facilities are not available in many places. In
of Neurology, categorizing the type of stroke is essential to a stroke, the biomarker work is based on the
1
Biostatistics and provide exact therapy.[3,4] About 80% of strokes pathophysiological aspects of ischemic tissue
2
Neurobiochemistry, are ischemic and 15%–20% are hemorrhagic, damage and the possibility that a particular
All India Institute of with different therapeutic and prognostic protein will be high in serum after tissue damage.
Medical Sciences, implications. Differentiating stroke subtype is There could be markers of tissue damage,
New Delhi, India a critical step when planning therapeutic goals inflammation, endothelium or hemostasis. High
in the initial period as specific management throughput screening of many molecules is
Address for and treatment protocols are recommended for another way of looking for a biomarker. Other
correspondence:
Prof. Rohit Bhatia,
Department of Neurology, This is an open access journal, and articles are distributed under the terms
How to cite this article: Bhatia R, Warrier AR,
All India Institute of of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0
Sreenivas V, Bali P, Sisodia P, Gupta A, et al. Role
Medical Sciences, License, which allows others to remix, tweak, and build upon the work
non‑commercially, as long as appropriate credit is given and the new of Blood Biomarkers in Differentiating Ischemic
New Delhi, India. Stroke and Intracerebral Hemorrhage. Neurol India
creations are licensed under the identical terms.
E‑mail: rohitbhatia71@ 2020;68:824-9. 
yahoo.com For reprints contact: reprints@medknow.com

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Bhatia, et al.: Biomarkers in stroke

methods include genome or proteome methods and RNA Each patient was recruited as close to the index event upon
expression.[5‑9] However, limitations to the use of biomarkers presentation to the emergency and a blood sample was
stems from the fact that tissue damage may happen over drawn for biomarker analysis. The sample was immediately
time and blood brain barrier may impede the release of these centrifuged at 3000 rpm for 10 min and serum separated and
molecules into the blood stream. stored at  ‑80 C, till analysis. IL6 was measured by a solid
phase, competitive chemiluminescent enzyme immunoassay
Recent past has seen an increasing interest in this field with method using the Immulite, Siemens machine and BNP,
various groups around the world aiming at discovering the S100, GFAP, and NMDA receptor antibody nR2 subunits
ideal biomarker for a particular disease process. Some proteins were measured using the ELISA technique with commercial
have been promising, yet validation is poor and there is a lack kits. The data was entered in the microsoft excel format and
of sensitivity and specificity. Although studies have looked analyzed using Stata version 14.2. Continuous variables were
into various facets of stroke including diagnosis, severity, assessed using Student’s t test and categorical by Fisher’s exact
outcomes, etiology, and correlation with biomarkers like test. Data is expressed as mean SD or median (IQR) where
astroglial protein S100B, glial fibrillary acidic protein (GFAP), appropriate. ROC curves were drawn for each biomarker
neuron specific enolase  (NSE), vascular cell adhesion and sensitivity, specificity, positive predictive value  (PPV),
molecule (VCAM1), inter‑cellular adhesion molecule ICAM1, and negative predictive value  (NPV) measured against the
N‑methly‑d‑aspartate (NMDA) receptor antibodies and matrix clinical and imaging based gold standard diagnosis. Sensitivity,
metalloproteinases (MMP) and acute thrombosis molecules specificity and predictive values were calculated along with
like D‑dimer, fibrinogen, and von‑Willebrand factor  (vWF); 95% confidence intervals. Association of biomarker levels with
none has be found to be absolute and specific, although data is different etiologies was assessed using one-way analysis of
encouraging. They may not be specific to a process, the blood variance (ANOVA).
brain barrier (BBB) restricts release of these biomarkers into
the systemic circulation, and therefore may not correlate with
Results
stroke severity. The present study aimed at assessing a set of
biomarkers to help differentiate IS from ICH.
250 acute stroke patients were recruited into the study. Among
these, 187 were IS and 63 patients had ICH. Baseline variables
Methods are presented in Table 1. The mean age of IS patients was
55.70 ± 14.78 years and ICH was 59.12 ± 15.10 years. There were
This is a prospective study carried out at the Department 64.71% (121/187) males among IS and 60.3% (39/63) among
of Neurology, All India Institute of Medical Sciences,
ICH group. The median NIHSS was higher among patients
New  Delhi, India. The study was approved by the institute
with ICH and higher number of patients in the IS group were
ethics committee. Informed consent was taken from each
hypertensives. Coronary artery disease and atrial fibrillation
patient or his legally authorized representative. The primary
were significantly higher among patients with IS.
objective of this study was to compare levels of individual
blood markers S100 B, glial fibrillary acidic protein (GFAP),
Biomarker results
N‑methyl‑D Aspartate receptor antibody (NR2) subunit, brain
The observed values are presented in Tables 2 and 3. Table 2
natriuretic peptide (BNP), and interleukin 6 (IL6) between IS
depicts the mean and median values of biomarkers among
and ICH. The secondary objective was to see if any particular
the two groups. Table 3 depicts a comparison between the
biomarker correlated with specific stroke etiology as classified
two groups. Patients with extreme values were considered
using Trial of Org10172 in Acute Stroke Treatment (TOAST)
outliers and were removed from analysis for more homogenous
criteria.[10] Based on previously published observations, with an
results (S100 four, NR2 one, IL6 4). S100 values was higher in
alpha error of 5% and a 90% power, a sample size of 250 patients
was planned. This estimate includes the fact that in any stroke patients with ICH compared with IS (8 pg/ml versus 4.2 pg/ml
cohort, ischemic stroke would be about 75%–80% and ICH respectively, P = 0.003) and IL6 was higher in patients with
about 20%–25%.
Table 1: Comparison of baseline characteristics
Consecutive patients with acute stroke within 24 hours of among patients with IS and ICH
presentation were recruited in the study. The stroke was Variable IS (n=187) ICH (n=63) P
confirmed by clinical features and imaging including computed Mean age 55.70±14.78 59.83±13.41 0.05
tomography  (CT), CT angiogram or magnetic resonance Male 64.71%(121/187) 60.32% (38/63) 0.53
imaging (MRI), MR angiogram. Patients were divided into NIHSS Median (IQR) 10 (6‑15) 14 (12‑16) 0.0001
ischemic stroke (IS) and intracerebral hemorrhage (ICH) based NIHSS (mean) 10.92 (5.83) 14.19 (5.70) 0.0001
on imaging. Details of stroke onset time, demographics, stroke HT 126 (67.3)% 58 (92.06%) 0.0001
risk factors, imaging details, baseline stroke severity (using Smoking 65 (34.7%) 20 (31.75%) 0.66
National Institutes of Health Stroke Scale  (NIHSS) scale), Diabetes 16 (25.4%) 60 (32.09%) 0.31
therapy received, and etiology of stroke were recorded. Alcohol 13 (20.6%) 37 (19.79%) 0.88
Outcomes were assessed using modified Rankin score at
Tobacco chewing 6 (9.52%) 10 (5.35%) 0.24
three months. Patients with stroke >24 hours from onset, ICH
CAD 2 (3.17%) 33 (17.65%) 0.004
due to etiology other than hypertension, active infection, active
Atrial fibrillation 0 (0.00%) 30 (16.04%) 0.001
systemic inflammatory disease, current immunosuppressive
therapy, and neurological disease other than stroke including Median sample time‑h (IQR) 15 14 0.95
dementia, tumor, and infection were excluded. Past stroke 30 (16.04) 7 (11.11) 0.34

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Bhatia, et al.: Biomarkers in stroke

IS compared to ICH (12.9 pg/ml vs 8.76 pg/ml, P = 0.02). No 53.70–68.3), PPV of 35.5% (95% CI 26.6–45.10), and a NPV of
significant differences were found among the other biomarkers. 82.4% (95% CI 74.9–88.4) to diagnose ICH. The area under the
The area under the curve (AUC) for all biomarkers is outlined curve (AUC) of IL6 was 59% (95% CI 0.53–0.61, Figure 1). At a
in Table 4. AUC for S100 was 65% (95% CI 0.58–0.73, Figure 1). value of less than 11 pg/ml, IL6 had a sensitivity of 55.7% (95%
At a value of 5.5 pg/ml and above, S 100 had a sensitivity CI 42.4–68.5), specificity of 56.2% (95% CI 48.7–63.5), PPV of
of 61.9%  (95% CI 48.8–73.9), specificity of 61.2%  (95% CI 29.6% (95% CI 21.4–38.8) and NPV of 79.4 (95% CI 71.4–86.0)
to diagnose ICH. We assessed stratified values of S100 and
Table 2: Showing mean and median values of the IL6 to assess for the discriminatory ability to diagnose ICH.
various biomarkers among patients with IS and ICH Values higher than 5 pg/ml were significantly more in patients
Biomarkers IS ICH with ICH. Similarly, for IL6, value higher than 10 pg/ml was
S 100pg/ml (n=246, IS more among patients with IS. We combined the results of S100
183, ICH 63) and IL6, to assess if together they have better discriminatory
Mean±SD 15.82±36.73 24.219±44.84 ability to diagnose ICH when compared with IS. Levels were
Median (IQR) 4.2 (3.4‑9.2) 8.0 (4.5‑22) considered normal if S100 <5.5 pg/ml and IL6 >10 pg/ml or
GFAPng/ml (n=250,
abnormal if any one value was abnormal i.e: S100 >5.5 pg/ml
IS187, ICH63) and/or IL6 <10pg/ml. The abnormal value was seen among
Mean±SD 91.38% patients with ICH compared with 63.74% patients
1.31±3.37 2.09±4.73
Median (IQR) with IS (P = 0.001) with a sensitivity of 91.4%, specificity of
0.24 (0.24‑0.9) 0.3 (0.17‑1.8)
36.3%, PPV of 32.7% and a higher of 92.5%.
NR2ng/ml (n=249, IS186,
ICH 63)
We also assessed biomarker values along different time points
Mean±SD 4.81±3.52 5.08±3.26 of sample collection from index event although individual
Median (IQR) 4.62 (4.62‑6.92) 5.66 (1.98‑7.15) patients were not sampled periodically over time. No statistical
BNPpg/ml (n=250, IS differences were observed among the biomarkers with respect
187, ICH 63) to time. [Figure 2a and b] Using TOAST classification, levels
Mean±SD 221.00±315.39 167.78±201.85 of biomarkers were analyzed in various etiological subtypes.
Median (IQR) 65.26 (9.22‑287.01) 61.26 (9.63‑241.56) No statistically significant differences were observed among
IL6pg/ml (n=246, IS 185, various biomarkers and TOAST subtypes.
ICH 61)
Mean±SD 21.27±26.16 16.11±20.60 Discussion
Median (IQR) 12.9 (6.25‑24.2) 8.3 (4.87‑17.1)
IS: Ischemic stroke, ICH: Intracerebral hemorrhage, GFAP: Glial fibrillary A blood biomarker should ideally be sensitive, specific, highly
acidic protein; BNP: Brain natriuretic peptide; NR2: NMDA receptor subunit 2; accurate, reproducible, have good positive and negative
IL: Interleukin. *P=0.016 **P=0.017; ng: Nanogram; pg: Picogram
predictive values, be easy to interpret by clinicians, and
cost effective.[3‑5] There has been an interest in developing
Table 3: Comparison of values of biomarkers biomarkers to differentiate stroke from mimics, types of
between IS and ICH. (Wilcoxon rank‑sum test) stroke, establishing etiology, and outcomes in general. A panel
Biomarkers IS (Median/IQR) ICH (Median/IQR) P of proteins, S100 B, VWF, MMP9, VCAM or S100B or VWF,
S 100 pg/ml 4.2 (3.4‑9.2) 8.0 (4.5‑22) MMP9, BDNF, and MCP‑1 can differentiate IS from controls
<5 ng/ml 108 (59.02%) 24 (38.1%) 0.002 with a high sensitivity and specificity.[11,12] In a systematic
5‑10 ng/ml 31 (16.94%) 17 (26.98%) 0.016 review of blood biomarkers in the diagnosis of ischemic stroke,
>10ng/ml 44 (24.04%) 22 (34.92%) the authors observed that although all showed a high sensitivity
GFAP ng/ml 0.24 (0.24‑0.9) 0.3 (0.17‑1.8) 0.09 or specificity, there were significant limitations in the design
NR 2 ng/ml 4.62 (4.62‑6.92) 5.66 (1.98‑7.15) 0.40 and reporting of all studies.[9]
BNP pg/ml 65.26 (9.22‑287.01) 61.26 (9.63‑241.56) 0.97
IL6 pg/ml 12.9 (6.25‑24.2) 8.3 (4.87‑17.1) In a recently updated evidence review, the authors concluded
<5 ng/ml 25 (13.51) 18 (29.51) 0.01 that there is still not enough evidence to suggest that any
5‑10 ng/ml 54 (29.19) 15 (24.59) newer biomarkers could differentiate IS from other causes.[13]
>10 ng/ml 106 (57.3) 28 (45.9) 0.017 In a large multicentric study[14] (BRAIN, The Biomarker Rapid
GFAP: Glial fibrillary acidic protein; BNP: Brain natriuretic peptide; Assessment In Ischemic Injury Study), 1146 patients with
NR2: NMDA receptor subunit 2; IL: interleukin; ng: Nanogram; pg: Picogram symptoms suggestive of stroke were recruited from 17 centers.

Table 4: Discriminatory ability of various biomarkers to diagnose ICH

Biomarkers AUC Cut off Sensitivity 95% CI Specificity 95% CI PPV 95% CI NPV 95% CI
S 100 65% >5.5 61.9% (48.8 73.9) 61.2% (53.7‑68.3) 35.5% (26.6‑45.10 82.4% (74.9‑88.4)
GFAP 56% >0.3 54% (40.9‑66.6) 53.5% (46.1‑60.8) 28.1% (20.3‑37) 77.5% (69.3‑84.4)
NR 2 53% >5.2 55.6% (42.5‑68.1) 54.3% (46.9‑61.6) 29.2% (21.2‑38.2) 78.3% (70.2‑85.1)
BNP 49.8% >62 47.6% (34.9‑60.6) 49.7% (42.4‑57.1) 24.2% (17.0‑32.7) 73.8% (65.2‑81.2)
IL6 59% <11 55.7% (42.4‑68.5) 56.2% (48.7‑63.5) 29.6% (21.4‑38.8) 79.4 (71.4‑86.0)
AUC: Area under curve; GFAP: Glial fibrillary acidic protein; BNP: Brain natriuretic peptide; NR2: NMDA receptor subunit 2; IL: interleukin; S 100 pg/ml,
GFAP ng/ml, NR2 ng/ml, BNP pg/ml, IL6 pg/ml

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Bhatia, et al.: Biomarkers in stroke
a b
Figure 1: (a and b) ROC curves for sensitivity and specificity of S100 and IL6 to differentiate ischemic stroke and intracerebral hemorrhage (see text for details)
a
b although it could not reach a statistical significance (P = 0.09)
Figure 2: (a and b) Biomarker values with respect to time
Blood was analyzed for MMP9, BNP, D‑Dimer, and protein
S100. A diagnostic tool incorporating the values of matrix
metalloproteinase 9, brain natriuretic factor, D‑dimer, and
S‑100 into a composite score was sensitive for acute cerebral
ischemia. The multivariate model demonstrated modest
discriminative capabilities with an area under the receiver
operating characteristic curve of 0.76 for hemorrhagic stroke
and 0.69 for all stroke (likelihood test P < 0.001). When the
threshold for the logistic model was set at the first quartile,
this resulted in a sensitivity of 86% for detecting all stroke
and a sensitivity of 94% for detecting hemorrhagic stroke.
However, the specificity was only 36%. Moreover, results were
reproducible in a separate cohort tested on a point‑of‑care
platform. The authors concluded that these results suggest
that a biomarker panel may add valuable and time‑sensitive
diagnostic information in the early evaluation of stroke. Such
an approach is feasible on a point‑of‑care platform.
Few studies have attempted differentiation of IS from ICH.
In our current study, only S100 and IL6 had significant
discriminatory ability to diagnose ICH, albeit with a moderate
sensitivity and specificity and a higher negative predictive
value. In a series of 135 patients (IS = 93, ICH = 42) assessed
within 6 hours of stroke onset GFAP  (glial fibrillary acidic
Neurology India | Volume 68 | Issue 4 | July-August 2020 827
protein) was detectable in the serum of 39 patients (34/42, 81%
with ICH and 5/93, 5% of IS). Serum GFAP was substantially
raised in patients with ICH compared with IS and was able to
differentiate IS from HS within six hours of onset with 79%
sensitivity, 98% specificity, PPV 94% and NPV of 91%, P < 0.001
with a ROC cut‑off of 2.9 ng/L levels.[15] Another study of
205 patients from 14 centers across Germany and Switzerland
aimed at studying GFAP as a candidate biomarker among ICH
patients, within 4.5 hours of onset of stroke.[16] Among 39 ICH
and 163 IS patients, GFAP concentrations were increased
in patients with ICH compared with patients with ischemic
stroke [median (interquartile range) 1.91 µg/L (0.41–17.66) vs
0.08 µg/L (0.02– 0.14), P < 0.001]. Diagnostic accuracy of GFAP
for differentiating ICH from I Sand stroke mimic was high [area
under the curve 0.915 (95% CI0.847– 0.982), P < 0.001]. A GFAP
cutoff of 0.29 µg/L provided diagnostic sensitivity of 84.2%
and diagnostic specificity of 96.3% for differentiating ICH
from IS and stroke mimic. In the present study, we found a
trend towards a higher GFAP levels, among patients with ICH,
even though the proportion of patients with ICH (n = 63) versus
IS (n = 189) were similar in the published study above. A larger
dataset may be required to validate this finding further. It could
also be related to timings of the sample collection as not all
patients could be sampled closest to the stroke time considering
there varied times of presentations to the hospital after the
index event. Timing from stroke onset has huge relevance in
case we wish to triage the patients for specific treatment and
blood biomarkers could vary with time duration.
Using CRP, D‑dimer, sRAGE, MMP9, S100B, BNP, NT‑3,
caspase 3, and chimerin –II, as biomarkers in 915 patients, the
authors in this study found significantly high levels of S100 and
reduced levels of sRAGE in patients with ICH.[5] The complete
protocol was achieved in 915 patients (776 IS, 139 ICH). Among
blood samples obtained <6 h from symptoms onset (n = 337),
S100B levels were increased in ICH (107.58 vs 58.70 pg/mL;
P  < 0.001), whereas sRAGE levels were decreased (0.77 vs
1.0 2ng/mL; P = 0.009) as compared to IS. In this subset of
patients S100 B  (OR 3.97  95% CI 1.82–8.68; P = 0.001) and
sRAGE (OR 0.22 95% CI 0.10–0.52;
P < 0.001) were independently associated with ICH. A regression
tree was created by CART method showing a good classification
ability (AUC = 0.762). Similar results were found for samples
obtained within three hours. The authors concluded that a
combination of biomarkers including those of the S100B/
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Bhatia, et al.: Biomarkers in stroke
RAGE pathway seems promising to achieve a rapid biochemical
diagnosis of IS versus ICH in the first hours from symptoms
onset. We also found S100 to be a likely promising marker with
statistically higher levels among patients with ICH compared
with IS subjects. Upon stratification, values above 5ng/ml were
consistently high among patients with ICH versus IS. This
biomarker denotes neuronal injury and is therefore likely to be
increased in patients with ICH, which leads to more shearing
damage to brain tissue. However, the same results have not
been replicated in another study where 97 prospective stroke
patients  (86% IS and 14% ICH) in a multicenter design were
evaluated with blood levels of S100B, NSE, GFAP and coagulation
biomarker, activated protein C inhibitor complex  (APC‑PCI)
within 24 hours of onset.[17] There were no differences in
S100B (P = 0.13) and NSE (P = 0.67) levels between patients with
ischemic stroke or ICH. However, GFAP levels were significantly
higher in ICH patients (P = 0.0057). APC‑PCI levels were higher
in larger ischemic strokes (P = 0.020). The combination of GFAP
and APC‑PCI levels, in patients with NIHSS score more than
3, had a sensitivity and negative predictive value of 100% for
ICH  (P = 0.0052). The authors concluded that blood levels of
biomarkers GFAP and APC‑PCI, prior to neuroimaging, may
rule out ICH in a mixed stroke population. We also explored
if a combination of S100 and IL6 would be more diagnostic to
differentiate ICH from IS. It was observed that any one abnormal
value (based on combinations) increased the negative predictive
value to rule out ICH. In recent stroke‑chip study, using a
set of 21 biomarkers, the authors could only find N‑Terminal
Pro‑B‑Type natriuretic peptide to be an independent parameter
to differentiate IS from ICH.[18] Although this was a large
multicentric study, it failed to suggest many potential biomarkers
as promising to differentiate stroke from mimics and IS from ICH.
In a recent meta analysis, although activated rotein C‑ protein
C inhibitor complex  (APC‑PCI), glial fibrillary acidic
protein (GFAP) and a panel of APC‑PCI &GFAP and retinol
binding protein 4 (RBP4) &GFAP were found to have high
sensitivity and specificity for differentiating the two stroke
types, the authors felt that the data was yet not robust to
suggest its routine clinical use.[19] Preliminary studies of NR2
peptides (degradation products of NR2 receptors of NMDA)
as biomarkers supports there use in diagnosing stroke.
Following stroke, NR2 peptide levels rise. IgG antibodies to
the fragments of the NMDA receptor have been recognized
and can be detected in blood and is a potential biomarker.[20‑22]
However, NMDA‑R antibodies have also been associated
with hypertension, atherosclerosis, prior stroke, epilepsy,
and encephalitis. Thus, the specificity of these antibodies is
uncertain. We could not however, replicate this finding in
our study. In a recent study, vascular endothelial growth
factor  (VEGF) was observed to correlate with three months
outcome and stroke severity. The authors used a clinical
biomarker module by incorporating biomarker levels of VEGF
and clinical parameters to show a good prediction of three
months outcome.[23] Imaging characteristics of patients may
also reveal an underlying etiology.
The present study did not find a significant difference in
biomarker levels based on underlying etiology. It could
potentially be related to a smaller sample size or inability to
definitely characterize patients in a defined etiology. In a recent
observation, the authors found multiple vascular territory acute
828 Neurology India | Volume 68 | Issue 4 | July-August 2020
infarcts to be related to many causes although cardioembolism
remained the commonest.[24] Higher levels of NT‑proBNP have
been observed in patients with cardioembolic stroke.[25]
Our study has limitations. The samples were collected from
patients up to 24 hours from the index event. Although this
is more realistic and pragmatic as access to ideal ambulance
services are not available to many patients and pre‑stroke
notification processes may be far from ideal, yet, the ideal
biomarker should be assessed closest to stroke onset for its
stratification and timely referral. With the current treatment
for endovascular interventions being extended to 24 hours,
the utility may be of value. A larger sample size may require
validation and methods to detect these biomarkers need to be
made accessible using a rapid assay like an automated small
device using strip technology for wider application.
In conclusion, S100 and IL6 are potential biomarkers for further
study and validation. Studies for newer biomarkers with a
higher discriminatory ability or a combination of biomarkers
are required in the future for diagnostic use.
Acknowledgement Grant Support
Funded by Intramural research grant by the All India Institute
of Medical Sciences, New Delhi, India.
Financial support and sponsorship
Grant support under the acknowledgement section above.
Conflicts of interest
There are no conflicts of interest.
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