Table 1.
Emerging biomarkers and their potential utility reported in epilepsy.
| Biomarker | Sample Type | Potential Utility | Examples | Current Limitations |
|---|---|---|---|---|
| High-mobility group box 1 protein | Primarily cerebrospinal fluid (CSF), some serum | CSF concentrations were significantly higher in drug-refractory epilepsy and newly diagnosed epilepsy groups compared with other non-inflammatory neurological disorders groups [79]. Levels in CSF reported to be positively associated with seizure frequency [81]. |
HMGB1 | Conflicting reports for the utility of HMGB1 in blood, and the more invasive CSF remains preferred sample type |
| Neurofilaments | Serum or plasma | Elevated levels have been reported in patients with autoimmune epilepsy and in adults with post-stroke epilepsy when compared to single-seizure patients [82]. Study involving patients with Down syndrome reported near-significant elevation of NfL levels in patients with epilepsy compared to no epilepsy [83]. |
NfL | Not specific to epilepsy as NfLs are released into the blood stream following neuronal damage |
| Purines | peripheral blood | Acute seizures and epilepsy have been reported to be associated with increased blood purine levels [84]. Deficiency of adenosine has been associated with an increase in DNA methylation levels (proposed to be implicated in epileptogenesis) [85]. |
Adenosine | Not specific to seizures or epilepsy and the short half-life of purines in blood makes it a challenging biomarker target |
| microRNAs (miRNAs) | plasma | miRNAs reported to be dysregulated in the plasma of patients with intractable temporal lobe epilepsy [86]. | miR-93-5p, miR-199a-3p and miR-574-3p | Emerging field |
| DNA Methylation (Targeted) | brain tissue, peripheral blood | Significant promoter hypermethylation was detected in epileptic patients of some gene promoters when compared between healthy controls [87]. Differentially methylated regions (DMRs) in at imprinting sites has been associated with epilepsy [88]. |
CPA6
UBE3A |
Most targeted screens require knowing the target, which is useful for reclassification of variants, but not for screening |
| Global DNA Methylation | brain tissue, peripheral blood | Altered DNA methylation patterns in mesial temporal lobe epilepsy detected when compared to unaffected controls [89]. Blood DNA methylation episignatures have been described for syndromic syndromes with epilepsy [90]. |
ATRX, CHD2, EHMT1, KANSL1, KDM5C, WHS CNVs | Emerging field and limited episignatures exist for non-syndromic epilepsies |