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Page 2 of 11 Ghosh et al. Neuroimmunol Neuroinflammation 2018;5:38 I http://dx.doi.org/10.20517/2347-8659.2018.28

ejection fraction < 35%, and TACS, independently predicted unfavorable outcome and mortality. High mean arte-
rial blood pressure (MABP) and capillary blood glucose (CBG) at admission were significant predictors of stroke
severity, unfavorable outcome, and mortality. Out of 10 thrombolysed patients, two had mRS score ≥ 2 and 3 had
the post-thrombolysis hemorrhage. Thrombolysis significantly reduced the incidence of the unfavorable outcome,
but did not significantly affect death. All the biomarker levels at admission were significantly higher among patients
with severe stroke and those who subsequently had an unfavorable outcome. D-dimer levels significantly increased
and fibrinogen level significantly decreased following thrombolysis. Higher MABP, CBG, and fibrinogen levels at ad-
mission predicted significantly higher chance to develop hemorrhagic complications post thrombolysis.

Conclusion: Low ejection fraction, occurrence of TACS and the higher levels of the biomarkers under study pre-
dicted poor outcome. Higher mean CBG and MABP and raised fibrinogen levels predicted higher chance of post-
thrombolysis hemorrhage.

Keywords: First-ever ischemic stroke, thrombolysis, biomarkers, total anterior circulation stroke, fibrinogen

INTRODUCTION
Stroke is one of the leading causes of death and disability in India, which is facing the double burden of
communicable and non-communicable diseases. The estimated adjusted prevalence rate of stroke range
from 84-262/100,000 in rural to 334-424/100,000 in urban areas. The incidence rate is 119-145/100,000 based
[1]
on the recent population based studies. These values were higher than those of high-income countries .
[2]
Case fatality rates vary widely, the highest being 42% in Kolkata . Among patients presenting with the first-
[3]
ever stroke in the Mumbai registry, 80.2% were ischemic strokes and 17.7% were hemorrhagic strokes . In
the Trivandrum registry, 83.6% were ischemic strokes, 11.6% were intracerebral hemorrhages, and 4.8% were
[4]
subarachnoid hemorrhages . Thirty-two percent of the patients in the Kolkata registry had hemorrhagic
[5]
stroke, the highest reported so far from India . The proportion of patients receiving recombinant tissue
plasminogen activator (rtPA) is low in our country, being 11% (104 out of 967 patients) in the on-going Indo
USA National stroke registry, due to lack of trained personnel. Intraarterial and mechanical thrombolysis
[6]
was given in 3.5% (34 out of 967 patients) .
Age, stroke severity, stroke mechanism, infarct location, comorbid conditions, clinical findings, and related
complications influence stroke prognosis. Interventions such as thrombolysis, stroke unit care, and reha-
bilitation also influence the outcome of ischemic stroke. Knowledge of these prognostic factors enables the
clinician to make a reasonable prediction for each patient, to offer a rational treatment to the patients, and
[7]
to help the family members understand the disease course . Though clinical examination can excellently
assess the stroke patients and the disease progression, biomarkers would be valuable to identify the patients
at risk of severe disease, to guide treatment and to reasonably predict the prognosis. Though many such
proteins which are markers of brain tissue damage, inflammation, and coagulation/thrombosis are associ-
ated with ischemic stroke, their successful translation to a biomarker useful in clinical practice has proven
[8]
difficult due to the heterogeneity of ischemic stroke . Moreover, they are not specific to ischemic stroke, as
many other disease processes can damage brain tissue. The blood- brain barrier restrains the release of these
biomarkers into the systemic circulation; hence, their levels may not correlate with the infarct volume, given
[9]
that the anatomic locations of stroke have different impacts on blood-brain barrier breakdown . Markers
of ischemic brain injury include S100 calcium binding protein B (S-100B), neuron-specific enolase (NSE),
myelin basic protein, and glial fibrillary acidic protein. Several proteins involved in inflammation and im-
mune response have also been identified as biomarkers of ischemic stroke, including C-reactive protein (CRP),
interleukin-6, tissue necrosis factor-alpha, vascular cell adhesion protein 1, intercellular adhesion molecule
1, N-methyl-d-aspartate receptor antibodies and matrix metalloproteinases. Similarly, molecules involved in