Biomarkers as prognostic determinants of epilepsy after post-acute central nervous system insults: a systematic review and meta-analysis
Shubham Misra1, Erum Khan2, TuKiet Lam1, Rajarshi Mazumder3, Ece Eldem1, Kapil Gururangan4, L. Brian Hickman3, Vaibhav Goswami5, Melissa Funaro1, Joan Montaner6, Terence Quinn7, David Liebeskind3, Nishant K. Mishra1
1Yale University, 2B.J.Medical College,Ahmedabad, 3University of California Los Angeles, 4Icahn School of Medicine at Mount Sinai, 5Tower Health, 6Vall d’Hebron Institute of Research, 7University of Glasgow
Objective:
To conduct a systematic review of biofluid biomarkers to test their association with the risk of post-CNS insult epilepsy.
Background:
It remains unknown if there are shared common biological pathways of an epileptogenic mechanism associated with a range of cerebral insults i.e., stroke, traumatic brain injury, and infections; and if certain biological markers could predict the risk of post-CNS insult epilepsy.
Design/Methods:
We searched articles until January 25, 2022, in PubMed, Embase, PsycINFO, Google Scholar, and Web of Science. The primary outcome was the difference in mean biomarker levels in patients with post-CNS insult epilepsy compared to patients without post-CNS insult epilepsy. We used the modified quality score based on the Reporting Recommendations for Tumor Marker Prognostic Studies for risk of bias assessment. For each biomarker, the level difference was calculated using the pooled standardized mean difference (SMD) and 95% confidence intervals (CI). (PROSPERO CRD42021297110)
Results:
We included 22 studies of 1499 cases with post-CNS insult epilepsy and 7929 controls with no post-CNS insult epilepsy. They investigated 47 biomarkers in blood or cerebrospinal fluid (CSF). Of 22 studies, 21 had moderate-to-high risk of bias. A meta-analysis was possible for only 19 biomarkers. Only blood glucose levels in four studies were significantly higher in patients with post-stroke epilepsy (PSE) than in patients without PSE (SMD 0.44; CI 0.19 to 0.69). From individual studies, 15 biomarkers in blood and seven in CSF were significantly associated with post-CNS insult epilepsy.
Conclusions:
While several biomarkers were found to be associated with epilepsy due to CNS insults, we do not recommend using the reported biomarkers for use in clinical settings or clinical trials. A significant limitation of these studies is that they included fewer patients with CNS insults who developed post-cerebral insult epilepsy. Collaborative efforts to promote biomarker discovery are therefore warranted.