Table 2.
Molecular, imaging, and electrophysiologic prognostic/diagnostic biomarkers for epileptogenesis, severe drug-refractory epilepsy and pharmacological and surgical therapy response.
| Study design | Modality | Tissue | Analysis platform | Biomarker | AUC | Reference |
|---|---|---|---|---|---|---|
| Prognostic & Diagnostic biomarker for epileptogenesis | ||||||
| Rats which develop epilepsy vs. rats which do not develop epilepsy after electrical stimulation - induced SE | Molecular | Plasma | ELISA | Increased total HMGB1 | 1.00* | Walker et al. (2017) |
| Children with benign childhood epilepsies vs. controls | Molecular | Hair | ECLIA | Increased hair cortisol within 24 h after the 1st seizure | 0.817 | Stavropoulos et al. (2017) |
| Rats with or without epilepsy after hyperthermia-induced SE at P11 | Imaging | Brain tissue - amygdala, thalamus | T2 MRI | T2 relaxation time ⇩ in basolateral amygdala T2 relaxation time ⇩ in medial amygdala T2 relaxation time ⇩ in medial thalamus |
0.910 0.820 0.780 |
Choy et al. (2014) |
| Rats with or without increased seizure susceptibility in the PTZ test after TBI | Imaging | Brain tissue - amygdala, hippocampus, thalamus | T2-w DTI MRI | T1σ in S1 cortex T1σ in Prh cortex T2 in thalamus T1σ in HC | 0.881 0.929 0.893 0.857 |
Pitkänen and Immonen (2014) |
| P21 rats which develop epilepsy vs. P21 rats which do not develop epilepsy after systemic pilocarpine -induced SE | Imaging | Septal pole of the hippocampus | MRS | Increased hippocampal mIns/tCr on day 72 post-SE | 0.830 | Pascente et al. (2016) |
| Patients with vs. without epilepsy after TBI | Imaging | Cerebral cortex | Gadolinium-MRI | Area of gadolinium leakage around cortical lesion after TBI | 0.850 | Data by A Friedman in Pitkänen et al. (2016) |
| Rats with epilepsy vs. no epilepsy after lateral fluid-percussion induced TBI | Electrophysiology | Brain | Sleep-EEG | Shortening of the duration of sleep spindles occurring at transition from N3 to REM | 0.907 | Andrade et al. (2016) |
| HFOs differentiate rats which develop epilepsy after intrahippocampal kainite injection or lateral fluid-percussion injury from those that will not | Electrophysiology | Brain | EEG | Presence of HFOs during the first 2 post-injury weeks | no data | Bragin et al. (2004, 2017) |
| Diagnostic biomarker for epileptogenesis or Prognostic biomarker for development epilepsy in rodents with brain injury |
Mice with or without epilepsy after i.c.v. injection of albumin, TGF-β, or IL-6 Rats with or without epilepsy after photothrombotic stroke Rats with or without epilepsy after bilateral hippocampal electrical stimulation - induced SE |
Brain | Electrophysiology Theta dynamics in EEG on days 2-4 |
Absolute slope value of dynamic change in theta band Distance from the mean control group |
0.910 0.997 |
Milikovsky et al. (2017) |
| Patients with acute anterior circulation ischemic stroke developing epilepsy vs. not developing epilepsy | Electrophysiology | Brain | EEG | Background asymmetry Interictal epileptiform activity |
0.810 | Bentes et al. (2018) |
| Three models | Electrophysiology | Brain | EEG | Decrease in non-linear dynamics dimension in EEG/ECoG | ≥0.886 in different models | Rizzi et al. (2019) |
| Prognostic/Diagnostic biomarkers for progression of epilepsy (drug-refractoriness) or epileptogenicity | ||||||
| Patients with high (median ≥4 sz/month) vs. low (<4) seizure frequency undergoing temporal lobectomy with amygdalohippocampectomy due to intractable TLE | Molecular | Lateral temporal cortex | Affymetrix GeneChip Human Gene 1.0 ST Array | Relative down-regulation of 35 genes and up-regulation of 5 genes in ≥4 sz/month group | ≥0.904* * logistic regression |
McCallum et al. (2016) |
| Drug-sensitive vs. drug-refractory patients | Molecular | Plasma | ELISA | Total HBMG1 | 0.990 | Walker et al. (2017) |
| Patients with benign vs. refractory mTLE | Imaging | Brain tissue - temporal lobe grey and white matter | DTI MRI | ⇧ ipsilateral MD ⇩ ipsilateral FA ⇩ ipsilateral HC vol ipsilateral HS FA+HS |
0.670 0.770 0.670 0.660 0.768 |
Labate et al. (2015) |
| Diagnostic biomarker for localization of seizure onset zone (tissue epileptogenicity) |
Intrahippocampal kainate model of TLE and lateral FPI model of PTE in rat Seizure onset zone vs. other brain areas in humans evaluated for epilepsy surgery |
Brain | Electrophysiology iHC or iECEEG scalp EEG |
occurrence of HFOs stereotypical HFOs with waveform similarity Spikes x HFO |
no data |
Bragin et al. (1999) Liu et al. (2018) Roehri et al. (2018) |
| Predictive biomarker for antiepileptogenic treatment effect | ||||||
| Post-SE rats treated with vehicle vs. anakinra+BoxA+ifenprodil polytherapy | Molecular | Plasma | ELISA | Prevention in the increase in total HMGB1 | ≥0.900* | Walker et al. (2017) |
| Predictive biomarker for cure after epilepsy surgery | ||||||
| Patients undergoing temporal lobectomy with amygdalohippocampectomy due to intractable TLE with seizure-free vs. non-seizure-free outcome | Molecular | Lateral temporal cortex | Affymetrix GeneChip Human Gene 1.0 ST Array | Relative down-regulation of ZNF852 CDCP2 PRRT1 FLJ41170 and 7 RNA probes in sz-free subjects |
0.958* 0.941* 0.942* 0.908* * logistic regression |
Gallek et al. (2016) |
Abbreviations: AUC, area under the curve; DTI, diffusion tensor imaging; ECLIA, electrochemiluminecence assay; EEG, electroencephalogram; ELISA, enzyme linked immune assay; HFO, high-frequency oscillation; HMGB1, high-mobility group box 1 protein; i.c.v., intracerebroventricular; i.p., intraperitoneal; MRI, magnetic resonance imaging; mTLE, medial temporal lobe epilepsy; P, postnatal day; PTE, post-traumatic epilepsy; PTZ, pentylenetetrazol; SE, status epilepticus; T2, a time constant for the decay of transverse magnetization arising from natural interactions at the atomic or molecular levels; TBI, traumatic brain injury; TLE, temporal lobe epilepsy