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Table 1 Biomarkers for post-stroke epilepsy

From: Blood and CSF biomarkers for post-stroke epilepsy: a systematic review

Study

Duration of study

Biomarker

Study design

Case- control sample size

Sex and age

Duration of stroke

Assay used

Conclusion

Results

Limitation

Sensitivity

Specificity

Zhang et al.

2014

(China) [7]

September 2010 to April 2013

CD40

Case-control study

410 IS patients, 389 PSE patients, and 160 healthy controls

Males and females

48 h

Immunoassay, Real-time PCR analysis

The frequency of T allele and sCD40L level were significantly higher in PSE patients than in IS patients.

The T allele of the CD40 − 1C/T polymorphism may be associated with PSE susceptibility. The CD40/CD40L system is involved in the process of PSE.

Sample size is relatively small.

Cell experiments were not conducted to reveal the pathogenic mechanism

Abraira et al.

2020

(Spain) [8]

2012–2017

d-dimer,

Endostatin,

FasL,

S100B,

Hsc70,

APO CIII,

GroA,

IL-6,

NT-proBNP,

VAP-1,

vWF,

IGFBP-3,

TNF-R1,

NCAM

Nested case-control

45/752

(of 752 IS patients, 45 had PSE, and 707 were non-PSE or taken as control)

Males and females

6 h

Immunoassay

The high level of endostatin > 1.203 and low levels of Hsc70 and S100B < 1.364 had strong positive associations with PSE.

Increased level of endostatin and decreased levels of Hsc70 and S100B may be associated with PSE.

There can be a negative impact on the number of late seizures because of increased number of loss-of-follow up due to death.

Zhang et al.

2020

(China) [9]

June 2013 to June 2018

IL-1β

Nested case- control

107 IS patients with seizure recurrence, 131 IS patients without seizure recurrence

Males and females

54–73 years

Quantitative real-time PCR (qRT-PCR)

IL-1β expression level was higher in patients with seizure recurrence than in patients without recurrence.

IL-1β might be a useful biomarker for early discovery of recurrence after the first epileptic seizure in IS patients.

70.09%

87.02%

Fu et al.

2109

(China) [10]

2014 to 2018

TRPM6 rs2274924,

Mg2 + .

Case- control

378 PSE patients/420 stroke patients

Males and females

PCR analysis, ion selective electrode method

Among 3 genotypes (TT, CT, and CC) of TRPM6, the frequency of the CC genotype was significantly higher in the PSE patients than in the controls

The increased frequency of CC genotype was significantly associated with PSE.

Further studies are needed for the exact understanding of molecular mechanisms.

Eriksson et al.

2020

(UK) [11]

2013 to 2016

tau,

NFL, GFAP,

S100b, NSE

Case control

4 PSE patients with thrombectomy /86 IS patients with thrombectomy

Males and females

2 h, 24 h, 48 h, 72 h, and at three months.

Tau or GFAP kit Single molecule array (Simoa) 2.0 assays

Tau protein showed 100% sensitivity and 73% specificity. Other bio-markers (NFL, GFAP, S100B, and NSE) showed 100% sensitivity and 77%–93% specificity

All blood biomarkers displayed interesting sensitivity and specificity.

Small sample size

100%

Tau protien: 73%, NFL, GFAP, S100B, or NSE: 77–93%

Jia et al.

2020

(China) [12]

March 2013 to March 2018

IL-6 mRNA

Nested case control

105 PIS patients with recurrent seizures /104 PIS patients without recurrent seizures

Males and females

37–82 years.

qRT-PCR

The expression of IL-6 mRNA was higher in the case group than in the control group.

IL-6 was independently correlated with seizure recurrence in patients with the first post-ischemic stroke seizure

The study had a retrospective design. An unequivocal distribution of the follow-up period,

68.57%

75.00%.

Yang et al.

2014

(China) [13]

ALDH2 rs671

Case- control

225 PSE patients, 240 IS patients and 267 healthy controls

Males and females

Polymerase chain reaction-restriction fragment length polymorphism

The frequency of rs671 A allele was higher in the PSE patients compared to the IS patients.

There is a positive association between ALDH2 polymorphism and PSE.

The study did not provide exact role of ALDH2 in PSE

Wang et al.

2021

(China) [14]

January 2015 to December 2018

Neuropeptide Y

Case- control

78 PISE patients /86 IS patients

Males and females

24 h

ELISA detection

Neuropeptide Y was inversely associated with PSE.

There was a 62% risk reduction in PISE patients with every 5 ng/ml increment of serum NPY.

Short duration of study, and sample size of the study was small

84.62%

86.05%

  1. * ApoCIII apolipoprotein CIII, FasL Fas ligand, GroA growth-related oncogene α, Hsc70 Heat shock 70 kDa protein-8, IGFBP-3 insulin-like growth factor binding protein-3, IL-6 interleukin 6, NCAM neural cell adhesion molecule, NT-proBNP N-terminal Pro-B-type natriuretic peptide, S100B S100 calcium-binding protein B, TNF-R1 tumor necrosis factor, VAP-1 vascular adhesion protein-1, vWF von Willebrand factor, IL-1β Inter leucine- one beta, TRPM6 transient receptor potential cation channel subfamily M member 6, NFL neurofilament light, GFAP glial fibrillary acidic protein, S100B S100 calcium-binding protein B, NSE neuron-specific enolase, ALDH2 Mitochondrial aldehyde dehydrogenase 2, NPY Neuropeptide Y