Increased Serum S100B Levels in Patients With Epilepsy: A Systematic Review and Meta-Analysis Study

Abstract

Importance: Accumulating evidence suggests that serum levels of S100B may play a role in epilepsy. Objective: We performed a meta-analysis to quantitatively summarize the serum S100B data available for patients with epilepsy. Data source: Two independent researchers conducted a systematic investigation of the Harvard Hollis+, Open Gray, Clinicaltrials, Wanfangdata, and CNKI databases through Dec 6, 2018, for all studies published in English and Chinese. The search terms included S100B and calcium-binding protein B in combination with epilepsy. Study selection: Original studies and reported data from these search terms are included. Studies where data overlapped with other studies were excluded. Data extraction and synthesis: investigators extracted, pooled and analyzed data from the included studies using a fixed-effects model in the Comprehensive Meta-Analysis3.3 and R software. Main outcomes and measures: Peripheral blood levels of S100B in patients with epilepsy compared with controls. Aberrations in peripheral blood levels of S100B were hypothesized to be related to epilepsy. Results: a fixed-effects meta-analysis of all 18 studies, including 1,057 unique participants, indicated that patients with epilepsy had significantly increased peripheral blood levels of S100B compared to controls (Hedges g = 1.568, 95% CI =1.431–1.706, P < 0.001). Sensitivity analysis showed that no single study significantly influenced the overall association of peripheral blood levels of S100B and epilepsy. Most of the subgroup analyses, including those of country, assay type and publication language, demonstrated a statistically significant association between peripheral blood levels of S100B and epilepsy. Meta-regression analyses indicated that gender (regression coefficient [SE], −0.2524 [0.0641]; 95%CI, −0.3781 to −0.1267; P = 0.0001) and mean age (regression coefficient [SE], −0.1224 [0.0426]; 95% CI, −0.2058 to −0.0390; P = 0.0040) might present serum S100B reductions, but sample size, years, assay type, publication language and country did not show moderating effects on the effect sizes. Furthermore, the trim-and-fill method used to adjust for funnel plot asymmetry in our meta-analysis confirmed that a positive outcome is unlikely to be due to publication bias. Conclusion and relevance: the results of this meta-analysis provide evidence for a significant increase in serum S100B levels in patients with epilepsy. Serum S100B is the most worthwhile biomarker of epilepsy, which is helpful for the clinical diagnosis and prognosis of epilepsy.

Brain injury markers in new-onset seizures in adults: A pilot study

“…Several investigators have demonstrated elevated brain injury marker levels in epilepsy, but there is not much data on levels in adults with new-onset seizures. Our results are well in line with previous studies of elevated S100B levels in epilepsy [25][26][27], which indicate that this marker should be investigated further for biomarker potential early in the disease course and perhaps as a marker of seizure burden. Pathophysiologically, increased levels of S100B could result from disruption of the blood brain barrier [14,28,29].…”

Imbalance of Systemic Redox Biomarkers in Children with Epilepsy: Role of Ferroptosis

“…Recently, Shekh-Ahmad [ 21 ] compared the total antioxidant capacity (TAC) in plasma, cortex, and hippocampus of an epilepsy mouse model, and they found decreased TAC levels in all districts, with comparable increases after antioxidant treatment, indicating that the biochemical changes occurring in SNC can be reflected in blood. Blood biomarkers as a surrogate for brain neurophysiology in epilepsy have also been analyzed by Liang et al [ 33 ], who found elevated levels of blood S100B at seizure onset and after seizures in patients. Although more studies will be needed to demonstrate if defects in the CNS can be translated into blood biomarkers fluctuations, by this study, we explore the possibility that ferroptosis biomarkers can be an index of patient’s disease status and, potentially, progression.…”

Peripheral Blood and Salivary Biomarkers of Blood–Brain Barrier Permeability and Neuronal Damage: Clinical and Applied Concepts

“…A first study ( 67 ) demonstrated that blood S100B is elevated at seizure onset and after seizures, in support of the hypothesis that BBB damage may trigger a seizure ( 7 , 101 – 103 ). A systematic review analyzed 18 studies and a total of 1,057 subjects, indicating that epileptic patients displayed elevated S100B blood levels as compared to controls ( 104 ). Meta-regression analyses showed that gender and mean age can impact serum S100B levels ( 104 ).…”

“…A systematic review analyzed 18 studies and a total of 1,057 subjects, indicating that epileptic patients displayed elevated S100B blood levels as compared to controls ( 104 ). Meta-regression analyses showed that gender and mean age can impact serum S100B levels ( 104 ). Another study correlated MRI T1 peri-ictal imaging to blood S100B in drug-resistant epileptic patients, confirming the increase in BBB permeability during a seizure ( 105 ).…”